Multiple Myeloma
Conditions
Keywords
Myeloma, Multiple Myeloma, Relapsed Multiple Myeloma, Relapsed and Refractory Multiple Myeloma, Refractory Myeloma, Resistant Multiple Myeloma, Treatment-resistant Multiple Myeloma, Pomalidomide, Lenalidomide-resistant, Bortezomib-resistant
Brief summary
The purpose of this study is to compare efficacy and safety of pomalidomide in combination with low-dose dexamethasone versus high-dose dexamethasone in subjects with refractory or relapsed and refractory multiple myeloma.
Interventions
DRUGpomalidomide
4 mg pomalidomide capsules administered orally
DRUGDexamethasone
40 mg dexamethasone (or 20 mg for participants \> 75 years of age) tablets administered orally
Sponsors
Celgene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must be ≥ 18 years of age * Subjects must have documented diagnosis of multiple myeloma and have measurable disease * Subjects must have undergone prior treatment with ≥ 2 treatment lines of anti-myeloma therapy * Subjects must have either refractory or relapsed and refractory disease defined as documented disease progression during or within 60 days of completing their last myeloma therapy * All subjects must have received at least 2 consecutive cycles of prior treatment that included lenalidomide and bortezomib * All subjects must have failed treatment with both lenalidomide and bortezomib in one of the following ways: 1) Documented progressive disease on or within 60 days of completing treatment with lenalidomide and/or bortezomib, or 2) In case of prior response \[≥ partial response (PR)\] to lenalidomide or bortezomib, subjects must have relapsed within 6 months after stopping treatment with lenalidomide and/or bortezomib-containing regimens, or 3) Subjects who have not had a ≥ minimal response (MR) and have developed intolerance/toxicity after a minimum of two cycles of lenalidomide- and/or bortezomib-containing regimen * Patients must have received adequate prior alkylator therapy * Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 * Females of childbearing potential (FCBP) must not become pregnant for 28 days prior to initiation of study drug, during the study, and for 28 days after discontinuation * Females must agree to abstain from breastfeeding during study participation and 28 days after study drug discontinuation * Males must agree to use a latex condom during any sexual during the study and for 28 days following discontinuation from this study * Males must also agree to refrain from donating semen or sperm while on pomalidomide and for 28 days after discontinuation from this study
Exclusion criteria
* Any of the following laboratory abnormalities: * Absolute neutrophil count (ANC) \< 1,000/μL * Platelet count \< 75,000/ μL for subjects in whom \< 50% of bone marrow nucleated cells are plasma cells * Creatinine clearance \< 45 mL/min * Corrected serum calcium \> 14 mg/dL * Hemoglobin ≤ 8 g/dL * Serum glutamic oxaloacetic transaminase (SGOT)/ aspartate aminotransferase (AST) or transaminase, serum glutamic pyruvic (SGPT)/ alanine aminotransferase (ALT) \> 3.0 x upper limit of normal (ULN) * Serum total bilirubin \> 2.0 mg/dL * Previous therapy with pomalidomide * Hypersensitivity to thalidomide, lenalidomide, or dexamethasone * Resistance to high-dose dexamethasone used in the last line of therapy * Peripheral neuropathy ≥ Grade 2 * Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant * Subjects who are planning for or who are eligible for stem cell transplant * Subjects with any one of the following: 1) Congestive heart failure, 2) Myocardial infarction within 12 months prior to starting study treatment, 3) Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris * Subjects who received any of the following within the last 14 days of initiation of study treatment: 1) Plasmapheresis, 2) Major surgery, 3) Radiation therapy, 4) Use of any anti-myeloma drug therapy * Use of any investigational agents within 28 days or 5 half-lives (whichever is longer) of treatment * Subjects with conditions requiring chronic steroid or immunosuppressive treatment * Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study * Incidence of gastrointestinal disease that may significantly alter the absorption of pomalidomide * Subjects unable or unwilling to undergo antithrombotic prophylactic treatment * Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subjects from signing the informed consent form * Pregnant or breastfeeding females * Known human immunodeficiency virus (HIV) positivity or active infectious hepatitis A, B, or C
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) - Primary Analysis | From randomization until the data cut-off date of 07 September 2012. Maximum duration of follow-up for PFS assessments was 57 weeks. | Progression-free survival was calculated as the time from randomization to disease progression as determined by the Independent Response Adjudication Committee based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier. Progressive disease required 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; • Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dl) attributed solely to plasma cell proliferative disease. |
| Progression-free Survival (PFS) With a Later Cut-off Date | From randomization until the data cut-off date of 01 March 2013. Maximum duration of follow-up for PFS assessments was 74 weeks. | Progression-free survival was calculated as the time from randomization to disease progression as determined by the Independent Response Adjudication Committee based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier. Progressive disease requires 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; • Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dl) attributed solely to plasma cell proliferative disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival With a Later Cut-off Date | From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up for survival was 93 weeks. | Overall survival is calculated as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented. |
| Overall Survival Based on the Final Dataset | From randomization until the data cut-off date of 29 August 2017. Maximum time on follow-up for survival was 324 weeks. | Overall survival is calculated as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented. |
| Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria | From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks. | Objective response is defined as a best overall response of stringent complete response (SCR), complete response (CR), very good partial response (VGPR) or partial response (PR) based on the Independent Response Adjudication Committee: SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level \< 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to \< 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required. |
| Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria | From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks. | Objective response defined as a best overall response of complete response (CR) or partial response (PR) based on the Independent Response Adjudication Committee: CR requires all of the following: - Absence of original monoclonal paraprotein in serum and urine by immunofixation maintained at least 42 days. - \<5% plasma cell in bone marrow aspirate and on bone marrow biopsy, if performed. - No increase in size or number of lytic bone lesions. - Disappearance of soft tissue plasmacytomas. PR requires all of the following: - ≥ 50% reduction in level of serum monoclonal paraprotein, maintained at least 42 days. - Reduction in 24-hour urinary light chain extraction by ≥ 90% or to \< 200 mg, maintained at least 42 days. - For patients with non-secretory myeloma, ≥ 50% reduction in plasma cells in bone marrow aspirate and on biopsy, if performed, for at least 42 days. - ≥ 50% reduction in the size of soft tissue plasmacytomas. - No increase in size or number of lytic bone lesions. |
| Time to Progression | From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks. | Time to progression (TTP) is calculated as the time from randomization to the first documented progression confirmed by a blinded, independent Response Adjudication Committee and based on the International Myeloma Working Group Uniform Response criteria (IMWG). Progressive disease requires 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; • Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dl) attributed solely to plasma cell proliferative disease. |
| Time to Response | From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks. | Time to response is calculated as the time from randomization to the initial documented response (partial response or better) based on IMWG criteria. SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level \< 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to \< 200 mg/24 hours. If present at baseline a ≥ 50% reduction in size of soft tissue plasmacytomas is also required. |
| Duration of Response | From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks. | Duration of response (calculated for responders only) is defined as time from the initial documented response (partial response or better) to confirmed disease progression, based on IMWG criteria assessed by the Independent Response Adjudication Committee. |
| Time to the First Hemoglobin Improvement | From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks. | Time to increased hemoglobin, defined as the time from randomization to at least one category improvement from Baseline in common terminology criteria for adverse events (CTCAE) grade for hemoglobin level. Hemoglobin categories are: 1) Normal; 2) CTCAE Grade 1: \< lower limit of normal (LLN) to 10.0 g/dL; 3) CTCAE Grade 2: \< 10.0 to \<8.0 g/dL. Participants with CTCAE Grade 3 anemia or worse at Baseline were excluded from the study. |
| Time to Improvement in Bone Pain | From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks. | Time to improvement in bone pain is defined as the time from randomization to at least one category improvement from Baseline in bone pain category. Bone pain was categorized (from best to worst) according to answers to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for patients with Multiple Myeloma Module (QLQ-MY20), Question 1, Have you had bone aches or pain?: 1) Not at all, 2) A little, 3) Quite a bit, or 4) Very much. |
| Time to Improvement in Renal Function | From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks. | Time to improvement in renal function is defined as the time from randomization to at least one category improvement from Baseline in renal function. Renal Function was categorized as (from best to worst): - Normal: creatinine clearance ≥80 mL/min; - Grade 1: creatinine clearance ≥60 to \<80 mL/min; - Grade 2 : creatinine clearance ≥45 to \< 60 mL/min. Participants with creatinine clearance \< 45 mL/min at baseline were excluded from the study. |
| Number of Participants With Adverse Events (AEs) | From first dose of study drug through to 30 days after the last dose as of the end of the study (29 August 2017); maximum time on treatment was 297, 269, and 239 weeks in the Pomalidomide + LD-Dex, HD-Dex, and cross-over groups respectively. | An adverse event is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A serious AE is any AE occurring at any dose that: • Results in death; • Is life-threatening; • Requires or prolongs existing inpatient hospitalization; • Results in persistent or significant disability/incapacity; • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0): Grade 1 = Mild (no limitation in activity or intervention required); Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required); Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); Grade 4 = Life-threatening; Grade 5 = Death. |
| Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain | Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6 | The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in QOL or functioning and positive values indicate improvement. |
| Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain | Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6 | The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Physical Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. |
| Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain | Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6 | The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. |
| Change From Baseline in the EORTC QLQ-C30 Fatigue Domain | Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6 | The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom). |
| Change From Baseline in the EORTC QLQ-C30 Pain Domain | Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6 | The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Pain Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reductions in pain (i.e. improvement in symptom) and positive values indicate increases in pain (i.e. worsening of symptom). |
| Change From Baseline in the European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms | Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6 | The European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients with Multiple Myeloma (EORTC QLQ-MY20) is a 20-question tool used in clinical research to assess health-related quality of life in multiple myeloma patients. The QLQ-MY20 includes four domains (Disease Symptoms, Side-Effects of Treatment, Body Image and Future Perspective). The EORTC QLQ-MY20 Disease Symptoms Scale is scored between 0 and 100, with a high score reflecting a higher level of symptoms. Negative change from Baseline values indicate reduction (i.e. improvement) in symptoms and positive values indicate increase (i.e. worsening) of symptoms. |
| Change From Baseline in the EORTC QLQ-MY20 Side Effects Domain | Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6 | The European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients with Multiple Myeloma (EORTC QLQ-MY20) is a 20-question tool used in clinical research to assess health-related quality of life in multiple myeloma patients. The QLQ-MY20 includes four domains (Disease Symptoms, Side-Effects of Treatment, Body Image and Future Perspective). The EORTC QLQ-MY20 Side Effects Scale is scored between 0 and 100, with a high score reflecting a higher level of symptoms. Negative change from Baseline values indicate reduction in side effects (i.e.improvement in symptom) and positive values indicate increase in side effects (i.e. worsening of symptom). |
| Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Utility Index Score | Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6 | EQ-5D is a self-administered questionnaire that assesses health-related quality of life (QOL). The EQ-5D descriptive health profile comprises five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 3 levels of response: No problem (1), some problems (2), and extreme problems (3). A unique EQ-5D health state is defined by combining one level from each of the five dimensions into a single utility index score. EQ-5D index values range from -0.59 to 1.00 where an EQ-5D score of 1.00 equals perfect health, a score of 0 equals death and a score of -0.59 equals worst imaginable health state. A positive change from Baseline score indicates improvement in health status. A negative change from Baseline score indicates worsening in health status. Negative scores represent the possible though unlikely situation that a patient's QOL is worse than death, i.e. they would rather be dead than living with that QOL |
| Time to First Worsening of Quality of Life (QOL) Domains | Assessed on Day 1 of the first 6 treatment cycles. | Time to worsening in quality of life domains was calculated as the time from Baseline to the first worsened minimally important difference (MID), defined as the smallest change in a QOL score considered important to patients that would lead the patient or clinician to consider a change in therapy. MID thresholds were calculated in Standard Error of Measurement (SEM) units using the Baseline QOL data. Based on the MID, participants were classified as worsened according to the following: For the EORTC QLQ-C30 global health status and functional scales and the EQ-5D health utility score, participants were classified as worsened if their change from Baseline score was less than -1 SEM. For the EORTC QLQ-C30 symptom scores (fatigue and pain) and EORTC QLQ-MY20 disease symptoms and side effects scales, participants were classified as worsened if their change from Baseline score was greater than 1 SEM. See previous outcome measures for definitions of each scale. |
| Time to Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status | From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks. | Time to improvement in ECOG performance status defined as the time from randomization until at least a one category improvement from Baseline in ECOG performance status score. The categories of the ECOG Performance Status Scale are as follows: -0: Fully active, able to carry on all pre-disease performance without restriction; -1: Restricted in physically strenuous activity but ambulatory and able to carry our work of a light or sedentary nature, e.g., light housework, office work; -2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. Patients with a score of 3, 4 or 5 were excluded from participating in the study. |
| Overall Survival - Primary Analysis | From randomization until the data cut-off date of 07 September 2012. Maximum time on follow-up for survival was 70 weeks. | Overall survival is calculated as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented. |
Countries
Australia, Belgium, Canada, Czechia, Denmark, France, Germany, Greece, Italy, Netherlands, Russia, Spain, Sweden, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 93 sites: 68 sites in Europe, 10 sites in Australia, 10 sites in Canada, 4 sites in Russia, and 1 site in the United States (US) from 18 March 2011 to 29 August 2017.
Pre-assignment details
Participants were randomized in a 2:1 ratio. Treatment phase discontinuation occurred when a participant had confirmed progressive disease. Participants who did not progress but who were intolerant to treatment, or no longer wished to receive study treatment entered the progression-free survival (PFS) follow-up period until disease progression.
Participants by arm
| Arm | Count |
|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants \> 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression. | 302 |
| High-Dose Dexamethasone Participants received 40 mg dexamethasone (participants \> 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression. | 153 |
| Total | 455 |
Baseline characteristics
| Characteristic | Total | Pomalidomide Plus Low-Dose Dexamethasone | High-Dose Dexamethasone |
|---|---|---|---|
| Age, Continuous | 63.6 years STANDARD_DEVIATION 9.4 | 63.6 years STANDARD_DEVIATION 9.33 | 63.7 years STANDARD_DEVIATION 9.56 |
| Age, Customized ≤ 75 Years Old | 419 Participants | 278 Participants | 141 Participants |
| Age, Customized > 75 Years Old | 36 Participants | 24 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 41 Participants | 27 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 332 Participants | 228 Participants | 104 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 82 Participants | 47 Participants | 35 Participants |
| Multiple Myeloma Stage before Study Entry Missing | 22 Participants | 14 Participants | 8 Participants |
| Multiple Myeloma Stage before Study Entry Stage I | 117 Participants | 81 Participants | 36 Participants |
| Multiple Myeloma Stage before Study Entry Stage II | 171 Participants | 115 Participants | 56 Participants |
| Multiple Myeloma Stage before Study Entry Stage III | 145 Participants | 92 Participants | 53 Participants |
| Participants with Prior Anti-Myeloma (MM) Therapies | 455 Participants | 302 Participants | 153 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 4 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 7 Participants | 4 Participants | 3 Participants |
| Race/Ethnicity, Customized Not collected | 83 Participants | 48 Participants | 35 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 357 Participants | 244 Participants | 113 Participants |
| Sex: Female, Male Female | 187 Participants | 121 Participants | 66 Participants |
| Sex: Female, Male Male | 268 Participants | 181 Participants | 87 Participants |
| Stratification Factor 2: Disease Population Disease Population Group 1 | 374 Participants | 249 Participants | 125 Participants |
| Stratification Factor 2: Disease Population Disease Population Group 2 | 13 Participants | 8 Participants | 5 Participants |
| Stratification Factor 2: Disease Population Disease Population Group 3 | 68 Participants | 45 Participants | 23 Participants |
| Stratification Factor 3: Number of Prior Anti-MM Therapies > 2 Prior Anti-MM Therapies | 430 Participants | 285 Participants | 145 Participants |
| Stratification Factor 3: Number of Prior Anti-MM Therapies 2 Prior Anti-MM Therapies | 25 Participants | 17 Participants | 8 Participants |
| Time from First Pathologic Diagnosis | 6.3 years STANDARD_DEVIATION 3.89 | 6.2 years STANDARD_DEVIATION 4.02 | 6.5 years STANDARD_DEVIATION 3.63 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 252 / 300 | 124 / 150 | 8 / 11 |
| other Total, other adverse events | 291 / 300 | 143 / 150 | 11 / 11 |
| serious Total, serious adverse events | 195 / 300 | 80 / 150 | 4 / 11 |
Outcome results
Primary
Progression-free Survival (PFS) - Primary Analysis
Progression-free survival was calculated as the time from randomization to disease progression as determined by the Independent Response Adjudication Committee based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier. Progressive disease required 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; • Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dl) attributed solely to plasma cell proliferative disease.
Time frame: From randomization until the data cut-off date of 07 September 2012. Maximum duration of follow-up for PFS assessments was 57 weeks.
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Progression-free Survival (PFS) - Primary Analysis | 15.7 weeks |
| High-Dose Dexamethasone | Progression-free Survival (PFS) - Primary Analysis | 8.0 weeks |
p-value: <0.00195% CI: [0.35, 0.59]Stratified Log Rank Test
Primary
Progression-free Survival (PFS) With a Later Cut-off Date
Progression-free survival was calculated as the time from randomization to disease progression as determined by the Independent Response Adjudication Committee based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier. Progressive disease requires 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; • Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dl) attributed solely to plasma cell proliferative disease.
Time frame: From randomization until the data cut-off date of 01 March 2013. Maximum duration of follow-up for PFS assessments was 74 weeks.
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Progression-free Survival (PFS) With a Later Cut-off Date | 16.0 weeks |
| High-Dose Dexamethasone | Progression-free Survival (PFS) With a Later Cut-off Date | 8.1 weeks |
p-value: <0.00195% CI: [0.39, 0.61]Stratified log-rank test
Secondary
Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Time frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Population: PRO population with available data at Baseline and each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain | Cycle 3, Day 1 | 2.40 units on a scale | Standard Deviation 20.36 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain | Cycle 5 Day 1 | 1.91 units on a scale | Standard Deviation 21.97 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain | Cycle 4, Day 1 | 2.44 units on a scale | Standard Deviation 21.05 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain | Cycle 6, Day 1 | 0.19 units on a scale | Standard Deviation 22.3 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain | Cycle 2, Day 1 | 1.22 units on a scale | Standard Deviation 21.44 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain | Cycle 6, Day 1 | -4.17 units on a scale | Standard Deviation 13.18 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain | Cycle 2, Day 1 | -2.87 units on a scale | Standard Deviation 21.57 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain | Cycle 3, Day 1 | -5.66 units on a scale | Standard Deviation 25.36 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain | Cycle 4, Day 1 | -6.31 units on a scale | Standard Deviation 23.48 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain | Cycle 5 Day 1 | -8.64 units on a scale | Standard Deviation 23.17 |
Secondary
Change From Baseline in the EORTC QLQ-C30 Fatigue Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).
Time frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Population: PRO population with available data at Baseline and each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Fatigue Domain | Cycle 3, Day 1 | 3.26 units on a scale | Standard Deviation 27.66 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Fatigue Domain | Cycle 5 Day 1 | 0.21 units on a scale | Standard Deviation 28.41 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Fatigue Domain | Cycle 4, Day 1 | 1.71 units on a scale | Standard Deviation 26.21 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Fatigue Domain | Cycle 6, Day 1 | 0.99 units on a scale | Standard Deviation 31.13 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Fatigue Domain | Cycle 2, Day 1 | 2.43 units on a scale | Standard Deviation 27.39 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Fatigue Domain | Cycle 6, Day 1 | 10.49 units on a scale | Standard Deviation 16.38 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Fatigue Domain | Cycle 2, Day 1 | 4.03 units on a scale | Standard Deviation 25.37 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Fatigue Domain | Cycle 3, Day 1 | 7.76 units on a scale | Standard Deviation 23.73 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Fatigue Domain | Cycle 4, Day 1 | 9.43 units on a scale | Standard Deviation 28.88 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Fatigue Domain | Cycle 5 Day 1 | 9.47 units on a scale | Standard Deviation 23 |
Secondary
Change From Baseline in the EORTC QLQ-C30 Pain Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Pain Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reductions in pain (i.e. improvement in symptom) and positive values indicate increases in pain (i.e. worsening of symptom).
Time frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Population: PRO population with available data at Baseline and each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Pain Domain | Cycle 3, Day 1 | -3.58 units on a scale | Standard Deviation 29.62 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Pain Domain | Cycle 5 Day 1 | -1.64 units on a scale | Standard Deviation 28 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Pain Domain | Cycle 4, Day 1 | -2.41 units on a scale | Standard Deviation 30.52 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Pain Domain | Cycle 6, Day 1 | -2.40 units on a scale | Standard Deviation 30.99 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Pain Domain | Cycle 2, Day 1 | -2.70 units on a scale | Standard Deviation 25.74 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Pain Domain | Cycle 6, Day 1 | 10.19 units on a scale | Standard Deviation 23.67 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Pain Domain | Cycle 2, Day 1 | 0.36 units on a scale | Standard Deviation 25.32 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Pain Domain | Cycle 3, Day 1 | 2.83 units on a scale | Standard Deviation 25.47 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Pain Domain | Cycle 4, Day 1 | 3.03 units on a scale | Standard Deviation 25.84 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Pain Domain | Cycle 5 Day 1 | 2.47 units on a scale | Standard Deviation 31.59 |
Secondary
Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Physical Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Time frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Population: PRO population with available data at Baseline and each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain | Cycle 3, Day 1 | -0.56 units on a scale | Standard Deviation 19.86 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain | Cycle 5 Day 1 | 0.91 units on a scale | Standard Deviation 19.92 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain | Cycle 4, Day 1 | 0.17 units on a scale | Standard Deviation 20.25 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain | Cycle 6, Day 1 | 0.54 units on a scale | Standard Deviation 21.3 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain | Cycle 2, Day 1 | -2.32 units on a scale | Standard Deviation 18.25 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain | Cycle 6, Day 1 | -4.81 units on a scale | Standard Deviation 14.24 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain | Cycle 2, Day 1 | -3.96 units on a scale | Standard Deviation 18.35 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain | Cycle 3, Day 1 | -9.69 units on a scale | Standard Deviation 16.67 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain | Cycle 4, Day 1 | -8.08 units on a scale | Standard Deviation 13.31 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain | Cycle 5 Day 1 | -5.43 units on a scale | Standard Deviation 19.31 |
Secondary
Change From Baseline in the EORTC QLQ-MY20 Side Effects Domain
The European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients with Multiple Myeloma (EORTC QLQ-MY20) is a 20-question tool used in clinical research to assess health-related quality of life in multiple myeloma patients. The QLQ-MY20 includes four domains (Disease Symptoms, Side-Effects of Treatment, Body Image and Future Perspective). The EORTC QLQ-MY20 Side Effects Scale is scored between 0 and 100, with a high score reflecting a higher level of symptoms. Negative change from Baseline values indicate reduction in side effects (i.e.improvement in symptom) and positive values indicate increase in side effects (i.e. worsening of symptom).
Time frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Population: PRO population with available data at Baseline and each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-MY20 Side Effects Domain | Cycle 3, Day 1 | 3.26 units on a scale | Standard Deviation 13.72 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-MY20 Side Effects Domain | Cycle 5 Day 1 | 4.74 units on a scale | Standard Deviation 14.45 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-MY20 Side Effects Domain | Cycle 4, Day 1 | 3.73 units on a scale | Standard Deviation 14.47 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-MY20 Side Effects Domain | Cycle 6, Day 1 | 4.55 units on a scale | Standard Deviation 15.76 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-MY20 Side Effects Domain | Cycle 2, Day 1 | 2.71 units on a scale | Standard Deviation 13.9 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-MY20 Side Effects Domain | Cycle 6, Day 1 | 7.30 units on a scale | Standard Deviation 9.35 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-MY20 Side Effects Domain | Cycle 2, Day 1 | 2.61 units on a scale | Standard Deviation 13.34 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-MY20 Side Effects Domain | Cycle 3, Day 1 | 5.35 units on a scale | Standard Deviation 12.27 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-MY20 Side Effects Domain | Cycle 4, Day 1 | 7.46 units on a scale | Standard Deviation 11.61 |
| High-Dose Dexamethasone | Change From Baseline in the EORTC QLQ-MY20 Side Effects Domain | Cycle 5 Day 1 | 6.89 units on a scale | Standard Deviation 10.32 |
Secondary
Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in QOL or functioning and positive values indicate improvement.
Time frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Population: The Patient Reported Outcomes (PRO) study population includes any intent-to-treat study participants with 1 active treatment and 1 PRO measurement item completed. Only participants with available data at Baseline and each time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain | Cycle 3, Day 1 | 2.67 units on a scale | Standard Deviation 24.97 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain | Cycle 5 Day 1 | 0.51 units on a scale | Standard Deviation 26.81 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain | Cycle 4, Day 1 | 0.80 units on a scale | Standard Deviation 24.62 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain | Cycle 6, Day 1 | -2.51 units on a scale | Standard Deviation 25.57 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain | Cycle 2, Day 1 | 0.52 units on a scale | Standard Deviation 23.01 |
| High-Dose Dexamethasone | Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain | Cycle 6, Day 1 | -0.93 units on a scale | Standard Deviation 17.59 |
| High-Dose Dexamethasone | Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain | Cycle 2, Day 1 | -3.75 units on a scale | Standard Deviation 24.1 |
| High-Dose Dexamethasone | Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain | Cycle 3, Day 1 | -2.36 units on a scale | Standard Deviation 21.08 |
| High-Dose Dexamethasone | Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain | Cycle 4, Day 1 | -3.03 units on a scale | Standard Deviation 22.42 |
| High-Dose Dexamethasone | Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain | Cycle 5 Day 1 | 0.00 units on a scale | Standard Deviation 27.44 |
Secondary
Change From Baseline in the European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms
The European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients with Multiple Myeloma (EORTC QLQ-MY20) is a 20-question tool used in clinical research to assess health-related quality of life in multiple myeloma patients. The QLQ-MY20 includes four domains (Disease Symptoms, Side-Effects of Treatment, Body Image and Future Perspective). The EORTC QLQ-MY20 Disease Symptoms Scale is scored between 0 and 100, with a high score reflecting a higher level of symptoms. Negative change from Baseline values indicate reduction (i.e. improvement) in symptoms and positive values indicate increase (i.e. worsening) of symptoms.
Time frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Population: PRO population with available data at Baseline and each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms | Cycle 3, Day 1 | -1.36 units on a scale | Standard Deviation 19.51 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms | Cycle 5 Day 1 | -0.53 units on a scale | Standard Deviation 17.39 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms | Cycle 4, Day 1 | -1.15 units on a scale | Standard Deviation 19.54 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms | Cycle 6, Day 1 | 0.60 units on a scale | Standard Deviation 19.64 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms | Cycle 2, Day 1 | -0.50 units on a scale | Standard Deviation 16.51 |
| High-Dose Dexamethasone | Change From Baseline in the European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms | Cycle 6, Day 1 | 2.12 units on a scale | Standard Deviation 13.43 |
| High-Dose Dexamethasone | Change From Baseline in the European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms | Cycle 2, Day 1 | -1.07 units on a scale | Standard Deviation 17.78 |
| High-Dose Dexamethasone | Change From Baseline in the European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms | Cycle 3, Day 1 | 0.97 units on a scale | Standard Deviation 19.93 |
| High-Dose Dexamethasone | Change From Baseline in the European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms | Cycle 4, Day 1 | 1.35 units on a scale | Standard Deviation 16.94 |
| High-Dose Dexamethasone | Change From Baseline in the European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms | Cycle 5 Day 1 | 1.48 units on a scale | Standard Deviation 17.56 |
Secondary
Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Utility Index Score
EQ-5D is a self-administered questionnaire that assesses health-related quality of life (QOL). The EQ-5D descriptive health profile comprises five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 3 levels of response: No problem (1), some problems (2), and extreme problems (3). A unique EQ-5D health state is defined by combining one level from each of the five dimensions into a single utility index score. EQ-5D index values range from -0.59 to 1.00 where an EQ-5D score of 1.00 equals perfect health, a score of 0 equals death and a score of -0.59 equals worst imaginable health state. A positive change from Baseline score indicates improvement in health status. A negative change from Baseline score indicates worsening in health status. Negative scores represent the possible though unlikely situation that a patient's QOL is worse than death, i.e. they would rather be dead than living with that QOL
Time frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Population: PRO population with available data at Baseline and each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Utility Index Score | Cycle 3, Day 1 | 0.01 units on a scale | Standard Deviation 0.29 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Utility Index Score | Cycle 5, Day 1 | 0.01 units on a scale | Standard Deviation 0.32 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Utility Index Score | Cycle 4, Day 1 | 0.04 units on a scale | Standard Deviation 0.31 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Utility Index Score | Cycle 6, Day 1 | 0.03 units on a scale | Standard Deviation 0.31 |
| Pomalidomide Plus Low-Dose Dexamethasone | Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Utility Index Score | Cycle 2, Day 1 | -0.03 units on a scale | Standard Deviation 0.28 |
| High-Dose Dexamethasone | Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Utility Index Score | Cycle 6, Day 1 | -0.12 units on a scale | Standard Deviation 0.19 |
| High-Dose Dexamethasone | Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Utility Index Score | Cycle 2, Day 1 | -0.02 units on a scale | Standard Deviation 0.23 |
| High-Dose Dexamethasone | Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Utility Index Score | Cycle 3, Day 1 | -0.06 units on a scale | Standard Deviation 0.27 |
| High-Dose Dexamethasone | Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Utility Index Score | Cycle 4, Day 1 | -0.07 units on a scale | Standard Deviation 0.29 |
| High-Dose Dexamethasone | Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Utility Index Score | Cycle 5, Day 1 | -0.04 units on a scale | Standard Deviation 0.26 |
Secondary
Duration of Response
Duration of response (calculated for responders only) is defined as time from the initial documented response (partial response or better) to confirmed disease progression, based on IMWG criteria assessed by the Independent Response Adjudication Committee.
Time frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Population: Intent-to-treat responder population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Duration of Response | 35.1 weeks |
| High-Dose Dexamethasone | Duration of Response | 28.1 weeks |
Secondary
Number of Participants With Adverse Events (AEs)
An adverse event is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A serious AE is any AE occurring at any dose that: • Results in death; • Is life-threatening; • Requires or prolongs existing inpatient hospitalization; • Results in persistent or significant disability/incapacity; • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0): Grade 1 = Mild (no limitation in activity or intervention required); Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required); Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); Grade 4 = Life-threatening; Grade 5 = Death.
Time frame: From first dose of study drug through to 30 days after the last dose as of the end of the study (29 August 2017); maximum time on treatment was 297, 269, and 239 weeks in the Pomalidomide + LD-Dex, HD-Dex, and cross-over groups respectively.
Population: Safety population (all randomized participants who received at least one dose of study drug (either pomalidomide or dexamethasone)).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | AE leading to discontinuation of either study drug | 38 Participants |
| Pomalidomide Plus Low-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | SAE leading to discontinuation of pomalidomide | 20 Participants |
| Pomalidomide Plus Low-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | Grade 3-4 AE related to either study drug | 212 Participants |
| Pomalidomide Plus Low-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | AE related to pomalidomide | 251 Participants |
| Pomalidomide Plus Low-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | SAE related to either study drug | 98 Participants |
| Pomalidomide Plus Low-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | Grade 5 adverse events | 46 Participants |
| Pomalidomide Plus Low-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | AE related to dexamethasone | 205 Participants |
| Pomalidomide Plus Low-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | SAE related to dexamethasone | 73 Participants |
| Pomalidomide Plus Low-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | Serious adverse events (SAEs) | 195 Participants |
| Pomalidomide Plus Low-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | Grade 3-4 adverse events | 266 Participants |
| Pomalidomide Plus Low-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | SAE related to pomalidomide | 89 Participants |
| Pomalidomide Plus Low-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | AE leading to discontinuation of pomalidomide | 30 Participants |
| Pomalidomide Plus Low-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | AE related to either study drug | 271 Participants |
| Pomalidomide Plus Low-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | Any adverse event | 298 Participants |
| Pomalidomide Plus Low-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | SAE leading to discontinuation of either study dru | 23 Participants |
| Pomalidomide Plus Low-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | Grade 3-4 AE related to pomalidomide | 199 Participants |
| Pomalidomide Plus Low-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | AE leading to discontinuation of dexamethasone | 34 Participants |
| Pomalidomide Plus Low-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | SAE leading to discontinuation of dexamethasone | 20 Participants |
| Pomalidomide Plus Low-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | Grade 3-4 AE related to dexamethasone | 114 Participants |
| High-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | AE leading to discontinuation of pomalidomide | 0 Participants |
| High-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | Any adverse event | 149 Participants |
| High-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | Grade 3-4 adverse events | 127 Participants |
| High-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | AE related to pomalidomide | 0 Participants |
| High-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | AE related to dexamethasone | 115 Participants |
| High-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | AE related to either study drug | 115 Participants |
| High-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | Grade 3-4 AE related to pomalidomide | 0 Participants |
| High-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | Grade 3-4 AE related to dexamethasone | 70 Participants |
| High-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | Grade 3-4 AE related to either study drug | 70 Participants |
| High-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | Grade 5 adverse events | 21 Participants |
| High-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | Serious adverse events (SAEs) | 80 Participants |
| High-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | SAE related to pomalidomide | 0 Participants |
| High-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | SAE related to dexamethasone | 36 Participants |
| High-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | SAE related to either study drug | 36 Participants |
| High-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | SAE leading to discontinuation of pomalidomide | 0 Participants |
| High-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | SAE leading to discontinuation of dexamethasone | 14 Participants |
| High-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | SAE leading to discontinuation of either study dru | 14 Participants |
| High-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | AE leading to discontinuation of dexamethasone | 16 Participants |
| High-Dose Dexamethasone | Number of Participants With Adverse Events (AEs) | AE leading to discontinuation of either study drug | 16 Participants |
| HD-Dex / Pomalidomide | Number of Participants With Adverse Events (AEs) | SAE related to either study drug | 1 Participants |
| HD-Dex / Pomalidomide | Number of Participants With Adverse Events (AEs) | Grade 3-4 AE related to dexamethasone | 2 Participants |
| HD-Dex / Pomalidomide | Number of Participants With Adverse Events (AEs) | AE leading to discontinuation of either study drug | 1 Participants |
| HD-Dex / Pomalidomide | Number of Participants With Adverse Events (AEs) | SAE leading to discontinuation of pomalidomide | 1 Participants |
| HD-Dex / Pomalidomide | Number of Participants With Adverse Events (AEs) | Grade 3-4 AE related to pomalidomide | 6 Participants |
| HD-Dex / Pomalidomide | Number of Participants With Adverse Events (AEs) | AE leading to discontinuation of dexamethasone | 1 Participants |
| HD-Dex / Pomalidomide | Number of Participants With Adverse Events (AEs) | SAE leading to discontinuation of dexamethasone | 1 Participants |
| HD-Dex / Pomalidomide | Number of Participants With Adverse Events (AEs) | AE related to either study drug | 11 Participants |
| HD-Dex / Pomalidomide | Number of Participants With Adverse Events (AEs) | Any adverse event | 11 Participants |
| HD-Dex / Pomalidomide | Number of Participants With Adverse Events (AEs) | SAE leading to discontinuation of either study dru | 1 Participants |
| HD-Dex / Pomalidomide | Number of Participants With Adverse Events (AEs) | AE related to dexamethasone | 5 Participants |
| HD-Dex / Pomalidomide | Number of Participants With Adverse Events (AEs) | Serious adverse events (SAEs) | 4 Participants |
| HD-Dex / Pomalidomide | Number of Participants With Adverse Events (AEs) | AE related to pomalidomide | 11 Participants |
| HD-Dex / Pomalidomide | Number of Participants With Adverse Events (AEs) | SAE related to pomalidomide | 1 Participants |
| HD-Dex / Pomalidomide | Number of Participants With Adverse Events (AEs) | Grade 5 adverse events | 1 Participants |
| HD-Dex / Pomalidomide | Number of Participants With Adverse Events (AEs) | AE leading to discontinuation of pomalidomide | 1 Participants |
| HD-Dex / Pomalidomide | Number of Participants With Adverse Events (AEs) | SAE related to dexamethasone | 0 Participants |
| HD-Dex / Pomalidomide | Number of Participants With Adverse Events (AEs) | Grade 3-4 AE related to either study drug | 6 Participants |
| HD-Dex / Pomalidomide | Number of Participants With Adverse Events (AEs) | Grade 3-4 adverse events | 8 Participants |
Secondary
Overall Survival Based on the Final Dataset
Overall survival is calculated as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.
Time frame: From randomization until the data cut-off date of 29 August 2017. Maximum time on follow-up for survival was 324 weeks.
Population: Intent-to-treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Overall Survival Based on the Final Dataset | 56.1 weeks |
| High-Dose Dexamethasone | Overall Survival Based on the Final Dataset | 35.3 weeks |
p-value: 0.00595% CI: [0.6, 0.91]Log Rank
Secondary
Overall Survival - Primary Analysis
Overall survival is calculated as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.
Time frame: From randomization until the data cut-off date of 07 September 2012. Maximum time on follow-up for survival was 70 weeks.
Population: Intent-to-treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Overall Survival - Primary Analysis | NA weeks |
| High-Dose Dexamethasone | Overall Survival - Primary Analysis | 34.0 weeks |
p-value: <0.00195% CI: [0.37, 0.74]Log Rank
Secondary
Overall Survival With a Later Cut-off Date
Overall survival is calculated as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.
Time frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up for survival was 93 weeks.
Population: Intent-to-treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Overall Survival With a Later Cut-off Date | 54.0 weeks |
| High-Dose Dexamethasone | Overall Survival With a Later Cut-off Date | 34.9 weeks |
p-value: 0.00995% CI: [0.54, 0.92]Log Rank
Secondary
Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria
Objective response is defined as a best overall response of stringent complete response (SCR), complete response (CR), very good partial response (VGPR) or partial response (PR) based on the Independent Response Adjudication Committee: SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level \< 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to \< 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.
Time frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Population: Intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria | 23.5 percentage of participants |
| High-Dose Dexamethasone | Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria | 3.9 percentage of participants |
p-value: <0.00195% CI: [3.19, 17.77]Fisher Exact
Secondary
Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria
Objective response defined as a best overall response of complete response (CR) or partial response (PR) based on the Independent Response Adjudication Committee: CR requires all of the following: - Absence of original monoclonal paraprotein in serum and urine by immunofixation maintained at least 42 days. - \<5% plasma cell in bone marrow aspirate and on bone marrow biopsy, if performed. - No increase in size or number of lytic bone lesions. - Disappearance of soft tissue plasmacytomas. PR requires all of the following: - ≥ 50% reduction in level of serum monoclonal paraprotein, maintained at least 42 days. - Reduction in 24-hour urinary light chain extraction by ≥ 90% or to \< 200 mg, maintained at least 42 days. - For patients with non-secretory myeloma, ≥ 50% reduction in plasma cells in bone marrow aspirate and on biopsy, if performed, for at least 42 days. - ≥ 50% reduction in the size of soft tissue plasmacytomas. - No increase in size or number of lytic bone lesions.
Time frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Population: Intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria | 22.2 percentage of participants |
| High-Dose Dexamethasone | Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria | 3.3 percentage of participants |
p-value: <0.00195% CI: [3.32, 21.42]Fisher Exact
Secondary
Time to First Worsening of Quality of Life (QOL) Domains
Time to worsening in quality of life domains was calculated as the time from Baseline to the first worsened minimally important difference (MID), defined as the smallest change in a QOL score considered important to patients that would lead the patient or clinician to consider a change in therapy. MID thresholds were calculated in Standard Error of Measurement (SEM) units using the Baseline QOL data. Based on the MID, participants were classified as worsened according to the following: For the EORTC QLQ-C30 global health status and functional scales and the EQ-5D health utility score, participants were classified as worsened if their change from Baseline score was less than -1 SEM. For the EORTC QLQ-C30 symptom scores (fatigue and pain) and EORTC QLQ-MY20 disease symptoms and side effects scales, participants were classified as worsened if their change from Baseline score was greater than 1 SEM. See previous outcome measures for definitions of each scale.
Time frame: Assessed on Day 1 of the first 6 treatment cycles.
Population: PRO population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Time to First Worsening of Quality of Life (QOL) Domains | Global Health Status | 71 days |
| Pomalidomide Plus Low-Dose Dexamethasone | Time to First Worsening of Quality of Life (QOL) Domains | Physical Functioning | 128 days |
| Pomalidomide Plus Low-Dose Dexamethasone | Time to First Worsening of Quality of Life (QOL) Domains | Emotional Functioning | 146 days |
| Pomalidomide Plus Low-Dose Dexamethasone | Time to First Worsening of Quality of Life (QOL) Domains | Fatigue | 58 days |
| Pomalidomide Plus Low-Dose Dexamethasone | Time to First Worsening of Quality of Life (QOL) Domains | Pain | 92 days |
| Pomalidomide Plus Low-Dose Dexamethasone | Time to First Worsening of Quality of Life (QOL) Domains | Disease Symptoms | 127 days |
| Pomalidomide Plus Low-Dose Dexamethasone | Time to First Worsening of Quality of Life (QOL) Domains | Side Effects of Treatment | 90 days |
| Pomalidomide Plus Low-Dose Dexamethasone | Time to First Worsening of Quality of Life (QOL) Domains | Health Utility | 225 days |
| High-Dose Dexamethasone | Time to First Worsening of Quality of Life (QOL) Domains | Health Utility | 162 days |
| High-Dose Dexamethasone | Time to First Worsening of Quality of Life (QOL) Domains | Global Health Status | 57 days |
| High-Dose Dexamethasone | Time to First Worsening of Quality of Life (QOL) Domains | Pain | 85 days |
| High-Dose Dexamethasone | Time to First Worsening of Quality of Life (QOL) Domains | Physical Functioning | 67 days |
| High-Dose Dexamethasone | Time to First Worsening of Quality of Life (QOL) Domains | Side Effects of Treatment | 85 days |
| High-Dose Dexamethasone | Time to First Worsening of Quality of Life (QOL) Domains | Emotional Functioning | 85 days |
| High-Dose Dexamethasone | Time to First Worsening of Quality of Life (QOL) Domains | Disease Symptoms | 106 days |
| High-Dose Dexamethasone | Time to First Worsening of Quality of Life (QOL) Domains | Fatigue | 57 days |
Secondary
Time to Improvement in Bone Pain
Time to improvement in bone pain is defined as the time from randomization to at least one category improvement from Baseline in bone pain category. Bone pain was categorized (from best to worst) according to answers to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for patients with Multiple Myeloma Module (QLQ-MY20), Question 1, Have you had bone aches or pain?: 1) Not at all, 2) A little, 3) Quite a bit, or 4) Very much.
Time frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Population: Intent-to-treat population with improvement in bone pain
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Time to Improvement in Bone Pain | 5.7 weeks |
| High-Dose Dexamethasone | Time to Improvement in Bone Pain | 4.1 weeks |
Secondary
Time to Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status
Time to improvement in ECOG performance status defined as the time from randomization until at least a one category improvement from Baseline in ECOG performance status score. The categories of the ECOG Performance Status Scale are as follows: -0: Fully active, able to carry on all pre-disease performance without restriction; -1: Restricted in physically strenuous activity but ambulatory and able to carry our work of a light or sedentary nature, e.g., light housework, office work; -2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. Patients with a score of 3, 4 or 5 were excluded from participating in the study.
Time frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Population: Intent-to-treat population with improvement in ECOG performance status during the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Time to Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status | 8.1 weeks |
| High-Dose Dexamethasone | Time to Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status | 4.3 weeks |
Secondary
Time to Improvement in Renal Function
Time to improvement in renal function is defined as the time from randomization to at least one category improvement from Baseline in renal function. Renal Function was categorized as (from best to worst): - Normal: creatinine clearance ≥80 mL/min; - Grade 1: creatinine clearance ≥60 to \<80 mL/min; - Grade 2 : creatinine clearance ≥45 to \< 60 mL/min. Participants with creatinine clearance \< 45 mL/min at baseline were excluded from the study.
Time frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Population: Intent-to-treat population with improvement in renal function
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Time to Improvement in Renal Function | 4.6 weeks |
| High-Dose Dexamethasone | Time to Improvement in Renal Function | 4.1 weeks |
Secondary
Time to Progression
Time to progression (TTP) is calculated as the time from randomization to the first documented progression confirmed by a blinded, independent Response Adjudication Committee and based on the International Myeloma Working Group Uniform Response criteria (IMWG). Progressive disease requires 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; • Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dl) attributed solely to plasma cell proliferative disease.
Time frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Time to Progression | 20.0 weeks |
| High-Dose Dexamethasone | Time to Progression | 9.0 weeks |
p-value: <0.00195% CI: [0.36, 0.59]Stratified Log Rank Test
Secondary
Time to Response
Time to response is calculated as the time from randomization to the initial documented response (partial response or better) based on IMWG criteria. SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level \< 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to \< 200 mg/24 hours. If present at baseline a ≥ 50% reduction in size of soft tissue plasmacytomas is also required.
Time frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Population: Intent-to-treat responder population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Time to Response | 8.1 weeks |
| High-Dose Dexamethasone | Time to Response | 10.5 weeks |
Secondary
Time to the First Hemoglobin Improvement
Time to increased hemoglobin, defined as the time from randomization to at least one category improvement from Baseline in common terminology criteria for adverse events (CTCAE) grade for hemoglobin level. Hemoglobin categories are: 1) Normal; 2) CTCAE Grade 1: \< lower limit of normal (LLN) to 10.0 g/dL; 3) CTCAE Grade 2: \< 10.0 to \<8.0 g/dL. Participants with CTCAE Grade 3 anemia or worse at Baseline were excluded from the study.
Time frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Population: Intent-to-treat population with improvement in hemoglobin during the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pomalidomide Plus Low-Dose Dexamethasone | Time to the First Hemoglobin Improvement | 3.4 weeks |
| High-Dose Dexamethasone | Time to the First Hemoglobin Improvement | 1.3 weeks |