Relapsed and/or Refractory Multiple Myeloma
Conditions
Keywords
Drug therapy
Brief summary
The main aim of this study is to learn if ixazomib, given with dexamethasone, stops the cancer from getting worse in people with relapsed or refractory multiple myeloma. It will be compared to another medicine called pomalidomide, given with dexamethasone with people with the same condition. Relapsed means the previous cancer treatment stopped working, over time. Refractory means they did not respond to previous cancer treatment. Another aim is to check for side effects from the study medicines. At the first visit, the study doctor will check who can take part. Participants who can take part will be picked for 1 of 2 treatments by chance. * Ixazomib capsules, given with dexamethasone tablets * Pomalidomide capsules, given with dexamethasone tablets All participants will take their study medicine on specific days during a 28-day cycle. The 1st dose of study medicines in each 28-day cycle will take place in the clinic, The other doses of the study medicines will be taken at home. This will happen for 6 cycles. After this, all study medicines will be taken at home. After treatment, participants will visit the clinic every 12 weeks for a check-up. If participants cannot attend their clinic for an important reason (for example, due to the COVID-19 pandemic), the clinic will make alternative arrangements using their local procedures.
Detailed description
The drug being tested in this study is called Ixazomib. Ixazomib is being tested to treat people who have relapsed and/or refractory multiple myeloma (RRMM). This study will compare the efficacy and safety in participants who take ixazomib and dexamethasone to pomalidomide and dexamethasone. It is an open-label, Phase 2 study. The study will enroll approximately 120 participants. Participants will receive: * Ixazomib 4 mg + dexamethasone 20 mg (or 10 mg if participant is aged \>=75 years) OR * Pomalidomide 4 mg + dexamethasone 40 mg (or 20 mg if participant is aged \>=75 years) All participants will be asked to take either ixazomib plus dexamethasone (in cases where only 4 mg tablets for dexamethasone are available, the following dexamethasone schedule is recommended for participants aged \>=75 years: 12 mg dexamethasone will be given on Days 1, 8, 15, and 22 of every 28-day cycle; and 8 mg dexamethasone will be given on Days 2, 9, 16, and 23 of every 28-day cycle) or pomalidomide 4 mg + dexamethasone 40 mg at recommended doses. This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 28 months after the first participant enters the study. Participants will make multiple visits to the clinic, and will be contacted for progression free-survival (PFS) follow-up, in case of study drug discontinuation for up to 4 years from first dose administration. After disease progression, participants will be followed-up for overall survival (OS) every 12 weeks until death or up to 4 years. Alternative methods for administering study procedures/assessments may be considered when it is not possible for the participants to come to the study site due to extenuating circumstances (e.g., due to the COVID-19 pandemic).
Interventions
DRUGIxazomib
Ixazomib capsules
DRUGPomalidomide
Pomalidomide capsules
DRUGDexamethasone
Dexamethasone tablets
Sponsors
Millennium Pharmaceuticals, Inc.
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
1. Must have a confirmed diagnosis of multiple myeloma (MM) requiring therapy according to International Myeloma Working Group (IMWG) criteria. 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 3. Must have had a relapse or progressive disease (PD) after having received 2 or more prior lines of systemic therapy. Note: A line of therapy is defined as 1 or more cycles of a planned treatment program; this may consist of 1 or more planned cycles of single-agent therapy or combination therapy, as well as a sequence of treatments administered in a planned manner. For example, a planned treatment approach of induction therapy followed by autologous stem cell transplantation (SCT), followed by maintenance is considered 1 line of therapy. Typically each line of therapy is separated by PD. Discussion with the medical monitor may help clarify the number of lines of therapy that a prospective study participant had. 4. Must be refractory to lenalidomide, defined as having received at least 2 consecutive cycles of lenalidomide as a single agent or within a lenalidomide-containing regimen and having had PD during treatment with or within 60 days after the last dose of lenalidomide. The starting dose of lenalidomide should have been 25 mg (or as low as 10 mg in the case of renal function impairment or other safety concern), and the final dose should have been a minimum of 10 mg. 5. Must have received at least 2 consecutive cycles of a bortezomib- or carfilzomib-containing regimen, and either: * Achieved at least a partial response (PR) and did not have PD during treatment with or within 60 days after the last dose of bortezomib or carfilzomib, OR * Had bortezomib and/or carfilzomib intolerance (defined as discontinuation because of drug-related adverse events \[AEs\] before completion of the planned treatment course) without PD before the start of the next regimen. 6. Must have measurable disease defined by: * Serum M-protein \>=1 g/dL (\>=10 g/L), OR * Urine M-protein \>=200 mg/24 hours and must have documented MM isotype by immunofixation (central laboratory). 7. Suitable venous access for the study-required blood sampling, including pharmacokinetic (PK) sampling. 8. Recovered (that is, less than or equal to \[\<=\] Grade 1 nonhematologic toxicity) from the reversible effects of prior anticancer therapy. 9. Must be willing and able to adhere to pomalidomide-related risk mitigation activities if randomized to the pom+dex arm (example, Risk Evaluation and Mitigation Strategies \[REMS\], pregnancy prevention programs).
Exclusion criteria
1. Prior allogenic bone marrow transplantation in any prior line of therapy or prior autologous SCT in the last prior line of therapy- unless the autologous SCT was performed a year or more before disease progression. 2. Diagnosed with or treated for another malignancy within 2 years before randomization, or previously diagnosed with another malignancy and have any evidence of residual, persistent, or recurrent disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection. 3. Diagnosis of smoldering MM, Waldenström's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome. 4. Peripheral neuropathy Grade 1 with pain or Grade 2 or higher peripheral neuropathy of any cause on clinical examination during the Screening period. 5. Treatment with any investigational products or with chimeric or fully human monoclonal antibodies within 30 days before randomization, systemic anticancer therapy or radiotherapy within 14 days before randomization (Note: spot radiation for areas of pain is permitted), and major surgery within 14 days before randomization. 6. Known gastrointestinal disease or gastrointestinal procedure that could interfere with the oral absorption or tolerance of study therapy, including difficulty swallowing. 7. Serious infection requiring parenteral antibiotic therapy or any other serious infection within 14 days before randomization. 8. Central nervous system involvement with MM (by clinical symptoms and signs). 9. Ongoing or active systemic infection, known human immunodeficiency virus-ribonucleic acid (RNA) positive, known hepatitis B surface antigen seropositive, or known hepatitis C virus-RNA positive. 10. Systemic treatment with strong cytochrome P-450 3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital) or use of St. John's wort within 14 days before randomization. 11. Admission or evidence of illicit drug use, drug abuse, or alcohol abuse. 12. History of severe cutaneous reactions, including hypersensitivity reactions such as Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), in the context of treatment with lenalidomide or thalidomide.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | From date of randomization until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years) | PFS: Time from randomization to first occurrence of confirmed progressive disease (PD) as assessed by investigator by International Myeloma Working Group(IMWG) response criteria/death from any cause, whichever occurs first. PD requires following: Increase of \>=25 % from nadir in: Serum M component (increase must be \>=0.5 gram per deciliter \[g/dl\]); Urine M-component (increase must be \>=200 milligram \[mg\]/24-hour); In participants without measurable serum and urine M-protein levels difference between involved and uninvolved free light chain (FLC) increase of \>10 mg/dl; In participants without measurable serum and urine M protein levels and without measurable disease by FLC level: bone marrow plasma cell percentage must be \>=10%; Development of new/increase in size of existing bone lesions/soft tissue plasmacytomas; development of hypercalcemia (\>11.5mg/dL corrected serum calcium) attributed solely to plasma cell proliferative disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Overall Response | From date of randomization until first documentation of CR, VGPR or PR (Up to approximately 3 years) | Overall Response Rate (ORR) was defined as the percentage of participants who achieved partial response (PR), very good partial response (VGPR), or complete response (CR) based on laboratory results and IRC assessment using modified IMWG criteria. PR: \>=50% reduction of serum M protein + reduction in 24-hour urinary M protein by \>=90% or to \<200 mg/24-hour; if M protein is not measurable, \>=50% decrease in difference between involved and uninvolved FLC levels is required; if not measurable by FLC, \>=50% reduction in bone marrow plasma cells, when baseline value \>=30% and; if present at baseline, \>=50% reduction in size of soft tissue plasmacytomas is required. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein + urine M-protein level \<100 mg/24-hour. CR: negative immunofixation on serum + urine; disappearance of soft tissue plasmacytomas; \<5 % plasma cells in bone marrow. |
| Duration of Response (DOR) | From date of first documentation of CR, VGPR or PR until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years) | DOR: Time from first documentation of CR/PR/VGPR to first documentation of PD. Per IMWG criteria, PR:\>=50% reduction of serum M protein+reduction in 24-hour urinary M protein by \>=90% to \<200 mg/24-hour or \>=50% decrease in difference between involved and uninvolved FLC levels/ \>=50% reduction in bone marrow plasma cells, if \>=30% at Baseline/ \>=50% reduction in size of soft tissue plasmacytomas. VGPR: serum+urine M-protein detectable by immunofixation but not on electrophoresis/ \>=90% reduction in serum M-protein + urine M-protein level \<100 mg/24-hour. CR:negative immunofixation on serum + urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow. PD:serum M-component increase \>=0.5 g/dl or urine M-component increase \>=200 mg/24-hour/ difference between involved and uninvolved FLC levels increase \>10 mg/dl or bone marrow plasma cell \>=10%/development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma or development of hypercalcemia. |
| Time to Response | From date of randomization until first documentation of CR, VGPR or PR (Up to approximately 3 years) | Time to response was defined as the time from randomization to the first documentation of PR/VGPR/CR. Per IMWG criteria, PR: \>=50% reduction of serum M protein + reduction in 24-hour urinary M protein by \>=90% or to \<200 mg/24-hour; if M-protein is not measurable, \>=50% decrease in difference between involved and uninvolved FLC levels is required; if not measurable by FLC, \>=50% reduction in bone marrow plasma cells, when Baseline value \>=30% and; if present at Baseline, \>=50% reduction in size of soft tissue plasmacytomas is required. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein + urine M-protein level \<100 mg/24-hour. CR: negative immunofixation on serum + urine; disappearance of soft tissue plasmacytomas; \<5% plasma cells in bone marrow. |
| Time to Progression (TTP) | From date of randomization until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years) | TTP was defined as the time from the date of randomization to first documentation of PD. Per IMWG criteria, PD required 1 of the following: Increase of \>=25% from nadir in: Serum M-component (increase must be \>=0.5 g/dl; Urine M-component (increase must be \>=200 mg/24-hour); In participants without measurable serum and urine M-protein levels difference between involved and uninvolved FLC levels increase of \>10 mg/dl; In participants without measurable serum and urine M protein levels and without measurable disease by FLC level: Bone marrow plasma cell percentage must be \>=10%; Development of new or increase in size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (\>11.5 mg/dL corrected serum calcium) attributed solely to plasma cell proliferative disease. |
| Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 (EORTC QLQ-C30) Physical Domain Score | Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days) | The EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/quality of life (QOL) scale. The physical domain consisted of 5 items covering participant's daily physical activities on a scale from 1 (not at all) to 4 (very much). Raw scores were linearly transformed to a total score between 0-100, with a high score indicating better physical functioning. |
| Overall Survival (OS) | From date of randomization to death due to any cause (Up to approximately 3 years) | OS was defined as the time from randomization to death from any cause, up to 3 years are reported. |
| HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score | Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days) | The EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 symptoms scales (disease symptoms, side effects of treatment), and 2 functional subscales (body image, future perspective). Scores were averaged and transformed to 0-100 scale. Higher scores for the future perspective scale indicate better perspective of the future, for the body image scale indicate better body image and for the disease symptoms scale indicate higher level of symptomatology. |
| Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | End of Treatment (Up to 28 cycles, each cycle was of 28 days) | EQ-5D-5L comprises of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each rated on 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, 5= extremely severe problems. Higher scores indicated greater levels of problems across the five dimensions. |
| HRQOL Based on EuroQol Visual Analogue Scale (EQ VAS) Score | Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days) | The EQ VAS records the respondent's self-rated health on a 20 centimeter (cm), vertical, visual analogue scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The scores from all dimensions were combined into a single index score that was reported, where higher score was better quality of life. |
| Health Care Utilization (HU): Number of Participants With at Least One Medical Encounter | Up to approximately 3 years | Healthcare resources used during medical encounters included hospitalizations, emergency room stays, or outpatient visits. A hospitalization was defined as at least 1 overnight stay in an Intensive Care Unit and/or non-Intensive Care Unit (acute care unit, palliative care unit, and hospice). |
| HU: Duration of Medical Encounters | Up to approximately 3 years | Duration of healthcare resources used during medical encounters including hospitalizations, emergency room stays, or outpatient visits was reported in days. A hospitalization was defined as at least 1 overnight stay in an Intensive Care Unit and/or non-Intensive Care Unit (acute care unit, palliative care unit, and hospice). |
| HRQOL Based on EORTC QLQ-C30 SubScale Score | Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days) | The EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a QOL scale. Most of the 30 items had 4 response levels (not at all, a little, quite a bit, and very much), with 2 questions relying on a 7-point numeric rating scale. Each subscale raw score were linearly transformed to a total score between 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL. The Physical domain of the functional subscale is reported in the secondary outcome measure 7. |
Countries
Australia, Belgium, Canada, Czechia, Denmark, France, Germany, Greece, Israel, Italy, Netherlands, Norway, Russia, Spain, Sweden, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study at 54 investigative sites in Australia, Turkey, Czech Republic, France, Germany, Italy, Netherlands, Norway, Spain, Israel, United Kingdom, Sweden, Greece, and Russian Federation from 01 August 2017 up to 26 November 2021.
Pre-assignment details
Participants with a diagnosis of relapsed and/or refractory multiple myeloma (RRMM) who received at least 2 prior lines of therapy were enrolled in 2:3 ratio to receive pomalidomide + dexamethasone or ixazomib + dexamethasone in this study.
Participants by arm
| Arm | Count |
|---|---|
| Pomalidomide 4 mg + Dexamethasone 40 mg Pomalidomide 4 mg, capsules, orally, once daily on Days 1 to 21 of each 28-day cycle, plus dexamethasone 40 mg, (or 20 mg if participant is aged \>=75 years), tablets, orally, once daily on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or sponsor termination of study up to 2 years. | 49 |
| Ixazomib 4 mg + Dexamethasone 20 mg Ixazomib 4 mg as starting dose, capsules, orally, once daily on Days 1, 8, and 15 of each 28-day cycle, with escalation to 5.5 mg at the start of Cycle 2 for participants who tolerated the 4 mg dose in Cycle 1, plus dexamethasone 20 mg (or 10 mg if participant is aged \>=75 years), tablets, orally, once daily on Days 1, 2, 8, 9, 15, 16, 22, and 23 of every 28-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or sponsor termination of study up to 2 years. | 73 |
| Total | 122 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 17 | 29 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Reason not Specified | 28 | 36 |
| Overall Study | Withdrawal by Subject | 4 | 7 |
Baseline characteristics
| Characteristic | Ixazomib 4 mg + Dexamethasone 20 mg | Pomalidomide 4 mg + Dexamethasone 40 mg | Total |
|---|---|---|---|
| Age, Continuous | 70.6 years STANDARD_DEVIATION 8.6 | 67.7 years STANDARD_DEVIATION 8.33 | 69.4 years STANDARD_DEVIATION 8.58 |
| Baseline Body Surface Area | 1.837 m^2 STANDARD_DEVIATION 0.243 | 1.864 m^2 STANDARD_DEVIATION 0.2203 | 1.848 m^2 STANDARD_DEVIATION 0.2336 |
| Baseline Height | 165.01 cm STANDARD_DEVIATION 10.475 | 166.59 cm STANDARD_DEVIATION 8.74 | 165.65 cm STANDARD_DEVIATION 9.808 |
| Baseline Weight | 74.36 kg STANDARD_DEVIATION 17.426 | 75.75 kg STANDARD_DEVIATION 16.16 | 74.92 kg STANDARD_DEVIATION 16.875 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 65 Participants | 42 Participants | 107 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 5 Participants | 10 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) White | 69 Participants | 46 Participants | 115 Participants |
| Region of Enrollment Australia | 6 Participants | 4 Participants | 10 Participants |
| Region of Enrollment Czechia | 3 Participants | 1 Participants | 4 Participants |
| Region of Enrollment France | 9 Participants | 3 Participants | 12 Participants |
| Region of Enrollment Germany | 6 Participants | 1 Participants | 7 Participants |
| Region of Enrollment Greece | 3 Participants | 0 Participants | 3 Participants |
| Region of Enrollment Ireland | 6 Participants | 3 Participants | 9 Participants |
| Region of Enrollment Israel | 2 Participants | 3 Participants | 5 Participants |
| Region of Enrollment Italy | 5 Participants | 9 Participants | 14 Participants |
| Region of Enrollment Netherlands | 2 Participants | 2 Participants | 4 Participants |
| Region of Enrollment Norway | 8 Participants | 7 Participants | 15 Participants |
| Region of Enrollment Russia | 15 Participants | 8 Participants | 23 Participants |
| Region of Enrollment Spain | 4 Participants | 2 Participants | 6 Participants |
| Region of Enrollment Sweden | 1 Participants | 2 Participants | 3 Participants |
| Region of Enrollment Turkey | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Female | 38 Participants | 23 Participants | 61 Participants |
| Sex: Female, Male Male | 35 Participants | 26 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 17 / 49 | 29 / 73 |
| other Total, other adverse events | 45 / 47 | 62 / 72 |
| serious Total, serious adverse events | 26 / 47 | 40 / 72 |
Outcome results
Primary
Progression Free Survival (PFS)
PFS: Time from randomization to first occurrence of confirmed progressive disease (PD) as assessed by investigator by International Myeloma Working Group(IMWG) response criteria/death from any cause, whichever occurs first. PD requires following: Increase of \>=25 % from nadir in: Serum M component (increase must be \>=0.5 gram per deciliter \[g/dl\]); Urine M-component (increase must be \>=200 milligram \[mg\]/24-hour); In participants without measurable serum and urine M-protein levels difference between involved and uninvolved free light chain (FLC) increase of \>10 mg/dl; In participants without measurable serum and urine M protein levels and without measurable disease by FLC level: bone marrow plasma cell percentage must be \>=10%; Development of new/increase in size of existing bone lesions/soft tissue plasmacytomas; development of hypercalcemia (\>11.5mg/dL corrected serum calcium) attributed solely to plasma cell proliferative disease.
Time frame: From date of randomization until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years)
Population: ITT Population included all participants who were randomized. Participants without documentation of PD were censored at the date of last response assessment that is stable disease (SD) or better.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pomalidomide 4 mg + Dexamethasone 40 mg | Progression Free Survival (PFS) | 4.8 months |
| Ixazomib 4 mg + Dexamethasone 20 mg | Progression Free Survival (PFS) | 7.1 months |
p-value: =0.47795% CI: [0.535, 1.341]Log Rank
Secondary
Duration of Response (DOR)
DOR: Time from first documentation of CR/PR/VGPR to first documentation of PD. Per IMWG criteria, PR:\>=50% reduction of serum M protein+reduction in 24-hour urinary M protein by \>=90% to \<200 mg/24-hour or \>=50% decrease in difference between involved and uninvolved FLC levels/ \>=50% reduction in bone marrow plasma cells, if \>=30% at Baseline/ \>=50% reduction in size of soft tissue plasmacytomas. VGPR: serum+urine M-protein detectable by immunofixation but not on electrophoresis/ \>=90% reduction in serum M-protein + urine M-protein level \<100 mg/24-hour. CR:negative immunofixation on serum + urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow. PD:serum M-component increase \>=0.5 g/dl or urine M-component increase \>=200 mg/24-hour/ difference between involved and uninvolved FLC levels increase \>10 mg/dl or bone marrow plasma cell \>=10%/development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma or development of hypercalcemia.
Time frame: From date of first documentation of CR, VGPR or PR until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years)
Population: Response Evaluable Population included all participants with multiple myeloma who had documentation of a confirmed PR, or PR/VGPR/CR. Only responders were reported for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pomalidomide 4 mg + Dexamethasone 40 mg | Duration of Response (DOR) | 14.3 months |
| Ixazomib 4 mg + Dexamethasone 20 mg | Duration of Response (DOR) | 14.8 months |
Secondary
Health Care Utilization (HU): Number of Participants With at Least One Medical Encounter
Healthcare resources used during medical encounters included hospitalizations, emergency room stays, or outpatient visits. A hospitalization was defined as at least 1 overnight stay in an Intensive Care Unit and/or non-Intensive Care Unit (acute care unit, palliative care unit, and hospice).
Time frame: Up to approximately 3 years
Population: ITT Population included all participants who were randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pomalidomide 4 mg + Dexamethasone 40 mg | Health Care Utilization (HU): Number of Participants With at Least One Medical Encounter | Hospitalizations | 16 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Health Care Utilization (HU): Number of Participants With at Least One Medical Encounter | Emergency Room Stays | 9 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Health Care Utilization (HU): Number of Participants With at Least One Medical Encounter | Outpatient Visits | 29 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Health Care Utilization (HU): Number of Participants With at Least One Medical Encounter | Hospitalizations | 23 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Health Care Utilization (HU): Number of Participants With at Least One Medical Encounter | Emergency Room Stays | 11 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Health Care Utilization (HU): Number of Participants With at Least One Medical Encounter | Outpatient Visits | 32 Participants |
Secondary
Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 (EORTC QLQ-C30) Physical Domain Score
The EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/quality of life (QOL) scale. The physical domain consisted of 5 items covering participant's daily physical activities on a scale from 1 (not at all) to 4 (very much). Raw scores were linearly transformed to a total score between 0-100, with a high score indicating better physical functioning.
Time frame: Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)
Population: ITT PRO Population included participants with a measurement at study entry and at least one post study entry measurement for at least 1 subscale on all 3 questionnaires (EORTC QLQ-C30, EORTC Multiple Myeloma Module 20 \[QLQ-MY20\] and EuroQol 5-Dimensional Health Questionnaire \[EQ-5D-5L\]). Number analyzed are the number of participants with data available for analyses at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pomalidomide 4 mg + Dexamethasone 40 mg | Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 (EORTC QLQ-C30) Physical Domain Score | Baseline | 67.0 score on a scale | Standard Deviation 21.97 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 (EORTC QLQ-C30) Physical Domain Score | End of Treatment | 52.4 score on a scale | Standard Deviation 28.03 |
| Ixazomib 4 mg + Dexamethasone 20 mg | Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 (EORTC QLQ-C30) Physical Domain Score | Baseline | 67.9 score on a scale | Standard Deviation 22.08 |
| Ixazomib 4 mg + Dexamethasone 20 mg | Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 (EORTC QLQ-C30) Physical Domain Score | End of Treatment | 56.5 score on a scale | Standard Deviation 26.1 |
Secondary
HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score
The EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 symptoms scales (disease symptoms, side effects of treatment), and 2 functional subscales (body image, future perspective). Scores were averaged and transformed to 0-100 scale. Higher scores for the future perspective scale indicate better perspective of the future, for the body image scale indicate better body image and for the disease symptoms scale indicate higher level of symptomatology.
Time frame: Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)
Population: ITT PRO Population included participants with a measurement at study entry and at least one post study entry measurement for at least 1 subscale on all 3 questionnaires (EORTC QLQ-C30, EORTC QLQ-MY20 and EQ-5D-5L). Number analyzed are the number of participants with data available for analyses at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score | Disease Symptoms: Baseline | 73.2 score on a scale | Standard Deviation 17.06 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score | Disease Symptoms: End of Treatment | 73.5 score on a scale | Standard Deviation 17.75 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score | Side Effects of Treatment: Baseline | 81.0 score on a scale | Standard Deviation 13.45 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score | Side Effects of Treatment: End of Treatment | 74.4 score on a scale | Standard Deviation 17.84 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score | Body Image: Baseline | 81.5 score on a scale | Standard Deviation 23.09 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score | Body Image: End of Treatment | 75.0 score on a scale | Standard Deviation 30.93 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score | Future Perspective: Baseline | 58.8 score on a scale | Standard Deviation 23.29 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score | Future Perspective: End of Treatment | 57.9 score on a scale | Standard Deviation 28.26 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score | Future Perspective: End of Treatment | 64.0 score on a scale | Standard Deviation 19.21 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score | Disease Symptoms: Baseline | 72.4 score on a scale | Standard Deviation 21.31 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score | Body Image: Baseline | 82.9 score on a scale | Standard Deviation 23.9 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score | Disease Symptoms: End of Treatment | 68.9 score on a scale | Standard Deviation 23.09 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score | Future Perspective: Baseline | 67.5 score on a scale | Standard Deviation 24.03 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score | Side Effects of Treatment: Baseline | 81.4 score on a scale | Standard Deviation 13.3 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score | Body Image: End of Treatment | 83.7 score on a scale | Standard Deviation 23.71 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score | Side Effects of Treatment: End of Treatment | 77.8 score on a scale | Standard Deviation 14.47 |
Secondary
HRQOL Based on EORTC QLQ-C30 SubScale Score
The EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a QOL scale. Most of the 30 items had 4 response levels (not at all, a little, quite a bit, and very much), with 2 questions relying on a 7-point numeric rating scale. Each subscale raw score were linearly transformed to a total score between 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL. The Physical domain of the functional subscale is reported in the secondary outcome measure 7.
Time frame: Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)
Population: ITT PRO Population included participants with a measurement at study entry and at least one post study entry measurement for at least 1 subscale on all 3 questionnaires (EORTC QLQ-C30, EORTC QLQ-MY20 and EQ-5D-5L). Number analyzed are the number of participants with data available for analyses at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Pain (Symptom Scale): Baseline | 61.1 score on a scale | Standard Deviation 30.77 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Emotional (Functional Scale): Baseline | 74.9 score on a scale | Standard Deviation 21.19 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Pain (Symptom Scale): End of Treatment | 51.2 score on a scale | Standard Deviation 26.42 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Social (Functional Scale): Baseline | 72.2 score on a scale | Standard Deviation 29.94 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Dyspnea (Symptom Scale): Baseline | 25.2 score on a scale | Standard Deviation 28.56 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Global Health Status/QoL: End of Treatment | 47.8 score on a scale | Standard Deviation 19.56 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Dyspnea (Symptom Scale): End of Treatment | 40.5 score on a scale | Standard Deviation 30.57 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Social (Functional Scale): End of Treatment | 63.1 score on a scale | Standard Deviation 27.35 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Insomnia (Symptom Scale): Baseline | 32.6 score on a scale | Standard Deviation 29.72 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Emotional (Functional Scale): End of Treatment | 67.6 score on a scale | Standard Deviation 25.19 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Insomnia (Symptom Scale): End of Treatment | 36.9 score on a scale | Standard Deviation 34.35 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Fatigue (Symptom Scale): Baseline | 60.0 score on a scale | Standard Deviation 22.89 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Appetite Loss (Symptom Scale): Baseline | 22.2 score on a scale | Standard Deviation 27.52 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Role (Functional Scale): End of Treatment | 47.6 score on a scale | Standard Deviation 27.86 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Appetite Loss (Symptom Scale): End of Treatment | 34.5 score on a scale | Standard Deviation 34.52 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Fatigue (Symptom Scale): End of Treatment | 50.8 score on a scale | Standard Deviation 25.02 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Constipation (Symptom Scale): Baseline | 13.3 score on a scale | Standard Deviation 23.99 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Cognitive(Functional Scale): Baseline | 79.6 score on a scale | Standard Deviation 20.38 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Constipation (Symptom Scale): End of Treatment | 25.0 score on a scale | Standard Deviation 34.69 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Nausea/Vomiting (Symptom Scale): Baseline | 96.7 score on a scale | Standard Deviation 8.41 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Diarrhea (Symptom Scale): Baseline | 17.8 score on a scale | Standard Deviation 23.14 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Role (Functional Scale): Baseline | 67.4 score on a scale | Standard Deviation 28.42 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Diarrhea (Symptom Scale): End of Treatment | 19.0 score on a scale | Standard Deviation 26.34 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Nausea/Vomiting (Symptom Scale): End of Treatment | 88.7 score on a scale | Standard Deviation 15.75 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Financial Difficulties (Symptom Scale): Baseline | 22.2 score on a scale | Standard Deviation 27.52 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Cognitive (Functional Scale): End of Treatment | 69.6 score on a scale | Standard Deviation 27.61 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Financial Difficulties (Symptom Scale): End of Treatment | 16.7 score on a scale | Standard Deviation 21.28 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Global Health Status/QoL: Baseline | 57.0 score on a scale | Standard Deviation 20.72 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Financial Difficulties (Symptom Scale): End of Treatment | 12.7 score on a scale | Standard Deviation 22.03 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Global Health Status/QoL: Baseline | 60.8 score on a scale | Standard Deviation 21.16 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Global Health Status/QoL: End of Treatment | 48.2 score on a scale | Standard Deviation 19.61 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Role (Functional Scale): Baseline | 67.9 score on a scale | Standard Deviation 29.67 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Role (Functional Scale): End of Treatment | 49.2 score on a scale | Standard Deviation 27.04 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Emotional (Functional Scale): Baseline | 83.1 score on a scale | Standard Deviation 21.7 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Emotional (Functional Scale): End of Treatment | 72.8 score on a scale | Standard Deviation 22.62 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Cognitive(Functional Scale): Baseline | 84.0 score on a scale | Standard Deviation 20.74 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Cognitive (Functional Scale): End of Treatment | 77.4 score on a scale | Standard Deviation 22.64 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Social (Functional Scale): Baseline | 75.7 score on a scale | Standard Deviation 27.02 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Social (Functional Scale): End of Treatment | 69.8 score on a scale | Standard Deviation 24.76 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Fatigue (Symptom Scale): Baseline | 61.0 score on a scale | Standard Deviation 23.07 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Fatigue (Symptom Scale): End of Treatment | 50.3 score on a scale | Standard Deviation 25.77 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Nausea/Vomiting (Symptom Scale): Baseline | 94.8 score on a scale | Standard Deviation 11.54 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Nausea/Vomiting (Symptom Scale): End of Treatment | 92.9 score on a scale | Standard Deviation 16.52 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Pain (Symptom Scale): Baseline | 65.2 score on a scale | Standard Deviation 24.7 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Pain (Symptom Scale): End of Treatment | 53.2 score on a scale | Standard Deviation 28.33 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Dyspnea (Symptom Scale): Baseline | 19.0 score on a scale | Standard Deviation 25.74 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Dyspnea (Symptom Scale): End of Treatment | 24.6 score on a scale | Standard Deviation 26.61 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Insomnia (Symptom Scale): Baseline | 29.5 score on a scale | Standard Deviation 31.87 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Insomnia (Symptom Scale): End of Treatment | 29.4 score on a scale | Standard Deviation 34.69 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Appetite Loss (Symptom Scale): Baseline | 14.3 score on a scale | Standard Deviation 22.39 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Appetite Loss (Symptom Scale): End of Treatment | 23.0 score on a scale | Standard Deviation 28.02 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Constipation (Symptom Scale): Baseline | 11.4 score on a scale | Standard Deviation 20.37 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Constipation (Symptom Scale): End of Treatment | 19.8 score on a scale | Standard Deviation 29.5 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Diarrhea (Symptom Scale): Baseline | 16.7 score on a scale | Standard Deviation 23.23 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Diarrhea (Symptom Scale): End of Treatment | 16.3 score on a scale | Standard Deviation 25.95 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EORTC QLQ-C30 SubScale Score | Financial Difficulties (Symptom Scale): Baseline | 17.1 score on a scale | Standard Deviation 25.85 |
Secondary
HRQOL Based on EuroQol Visual Analogue Scale (EQ VAS) Score
The EQ VAS records the respondent's self-rated health on a 20 centimeter (cm), vertical, visual analogue scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The scores from all dimensions were combined into a single index score that was reported, where higher score was better quality of life.
Time frame: Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)
Population: ITT PRO Population included participants with a measurement at study entry and at least one post study entry measurement for at least 1 subscale on all 3 questionnaires (EORTC QLQ-C30, EORTC QLQ-MY20 and EQ-5D-5L). Number analyzed are the number of participants with data available for analyses at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EuroQol Visual Analogue Scale (EQ VAS) Score | Baseline | 59.2 score on a scale | Standard Deviation 20.96 |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HRQOL Based on EuroQol Visual Analogue Scale (EQ VAS) Score | End of Treatment | 46.9 score on a scale | Standard Deviation 19.07 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EuroQol Visual Analogue Scale (EQ VAS) Score | Baseline | 64.4 score on a scale | Standard Deviation 18.21 |
| Ixazomib 4 mg + Dexamethasone 20 mg | HRQOL Based on EuroQol Visual Analogue Scale (EQ VAS) Score | End of Treatment | 55.9 score on a scale | Standard Deviation 19.6 |
Secondary
HU: Duration of Medical Encounters
Duration of healthcare resources used during medical encounters including hospitalizations, emergency room stays, or outpatient visits was reported in days. A hospitalization was defined as at least 1 overnight stay in an Intensive Care Unit and/or non-Intensive Care Unit (acute care unit, palliative care unit, and hospice).
Time frame: Up to approximately 3 years
Population: ITT Population included all participants who were randomized.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pomalidomide 4 mg + Dexamethasone 40 mg | HU: Duration of Medical Encounters | Hospitalizations | 2.0 days |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HU: Duration of Medical Encounters | Emergency Room Stays | 1.0 days |
| Pomalidomide 4 mg + Dexamethasone 40 mg | HU: Duration of Medical Encounters | Outpatient Visits | 4.0 days |
| Ixazomib 4 mg + Dexamethasone 20 mg | HU: Duration of Medical Encounters | Hospitalizations | 1.0 days |
| Ixazomib 4 mg + Dexamethasone 20 mg | HU: Duration of Medical Encounters | Emergency Room Stays | 1.0 days |
| Ixazomib 4 mg + Dexamethasone 20 mg | HU: Duration of Medical Encounters | Outpatient Visits | 3.0 days |
Secondary
Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score
EQ-5D-5L comprises of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each rated on 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, 5= extremely severe problems. Higher scores indicated greater levels of problems across the five dimensions.
Time frame: End of Treatment (Up to 28 cycles, each cycle was of 28 days)
Population: ITT PRO Population included participants with a measurement at study entry and at least one post study entry measurement for at least 1 subscale on all 3 questionnaires (EORTC QLQ-C30, EORTC QLQ-MY20 and EQ-5D-5L). Overall number of participants analyzed are the number of participants with data available for analyses.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Mobility: 3 = I Have Moderate Problems in Walking About | 8 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Usual Activities: 4 = I Have Severe Problems Doing my Usual Activities | 7 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Self-Care: 3 = I Have Moderate Problems Washing or Dressing Myself | 5 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Usual Activities: 5 = I am Unable to do my Usual Activities | 1 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Mobility: 5 = I am Unable to Walk About | 0 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Pain/Discomfort: 1 = I Have no Pain or Discomfort | 3 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Self-Care: 4 = I Have Severe Problems Washing or Dressing Myself | 3 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Pain/Discomfort: 2 = I Have Slight Pain or Discomfort | 5 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Mobility: 2 = I Have Slight Problems in Walking About | 6 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Pain/Discomfort: 3 = I Have Moderate Pain or Discomfort | 13 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Self-Care: 5 = I am Unable to Wash or Dress Myself | 0 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Pain/Discomfort: 4 = I Have Severe Pain or Discomfort | 6 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Self-Care: 1 = I Have no Problems Washing or Dressing Myself | 13 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Pain/Discomfort: 5 = I Have Extreme Pain or Discomfort | 0 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Usual Activities: 1 = I Have no Problems Doing my Usual Activities | 4 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Anxiety/Depression: 1 = I Have no Pain or Discomfort | 6 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Mobility: 4 = I Have Severe Problems in Walking About | 8 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Anxiety/Depression: 2 = I Have no Pain or Discomfort | 8 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Usual Activities: 2 = I Have Slight Problems Doing my Usual Activities | 7 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Anxiety/Depression: 3 = I Have no Pain or Discomfort | 11 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Self-Care: 2 = I Have Slight Problems Washing or Dressing Myself | 6 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Anxiety/Depression: 4 = I Have no Pain or Discomfort | 2 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Usual Activities: 3 = I Have Moderate Problems Doing my Usual Activities | 8 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Anxiety/Depression: 5 = I Have no Pain or Discomfort | 0 Participants |
| Pomalidomide 4 mg + Dexamethasone 40 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Mobility: 1 = I Have no Problems in Walking About | 5 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Anxiety/Depression: 5 = I Have no Pain or Discomfort | 2 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Mobility: 1 = I Have no Problems in Walking About | 9 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Mobility: 2 = I Have Slight Problems in Walking About | 12 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Mobility: 3 = I Have Moderate Problems in Walking About | 11 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Mobility: 4 = I Have Severe Problems in Walking About | 8 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Mobility: 5 = I am Unable to Walk About | 1 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Self-Care: 1 = I Have no Problems Washing or Dressing Myself | 21 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Self-Care: 2 = I Have Slight Problems Washing or Dressing Myself | 10 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Self-Care: 3 = I Have Moderate Problems Washing or Dressing Myself | 4 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Self-Care: 4 = I Have Severe Problems Washing or Dressing Myself | 4 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Self-Care: 5 = I am Unable to Wash or Dress Myself | 2 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Usual Activities: 1 = I Have no Problems Doing my Usual Activities | 10 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Usual Activities: 2 = I Have Slight Problems Doing my Usual Activities | 9 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Usual Activities: 3 = I Have Moderate Problems Doing my Usual Activities | 12 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Usual Activities: 4 = I Have Severe Problems Doing my Usual Activities | 7 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Usual Activities: 5 = I am Unable to do my Usual Activities | 3 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Pain/Discomfort: 1 = I Have no Pain or Discomfort | 8 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Pain/Discomfort: 2 = I Have Slight Pain or Discomfort | 10 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Pain/Discomfort: 3 = I Have Moderate Pain or Discomfort | 15 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Pain/Discomfort: 4 = I Have Severe Pain or Discomfort | 6 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Pain/Discomfort: 5 = I Have Extreme Pain or Discomfort | 2 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Anxiety/Depression: 1 = I Have no Pain or Discomfort | 19 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Anxiety/Depression: 2 = I Have no Pain or Discomfort | 13 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Anxiety/Depression: 3 = I Have no Pain or Discomfort | 6 Participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score | Anxiety/Depression: 4 = I Have no Pain or Discomfort | 1 Participants |
Secondary
Overall Survival (OS)
OS was defined as the time from randomization to death from any cause, up to 3 years are reported.
Time frame: From date of randomization to death due to any cause (Up to approximately 3 years)
Population: ITT Population included all participants who were randomized. Participants without documented death at the time of analysis were censored at the date last known to be alive.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pomalidomide 4 mg + Dexamethasone 40 mg | Overall Survival (OS) | NA months |
| Ixazomib 4 mg + Dexamethasone 20 mg | Overall Survival (OS) | 18.8 months |
p-value: =0.26595% CI: [0.761, 2.677]Log Rank
Secondary
Percentage of Participants With Overall Response
Overall Response Rate (ORR) was defined as the percentage of participants who achieved partial response (PR), very good partial response (VGPR), or complete response (CR) based on laboratory results and IRC assessment using modified IMWG criteria. PR: \>=50% reduction of serum M protein + reduction in 24-hour urinary M protein by \>=90% or to \<200 mg/24-hour; if M protein is not measurable, \>=50% decrease in difference between involved and uninvolved FLC levels is required; if not measurable by FLC, \>=50% reduction in bone marrow plasma cells, when baseline value \>=30% and; if present at baseline, \>=50% reduction in size of soft tissue plasmacytomas is required. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein + urine M-protein level \<100 mg/24-hour. CR: negative immunofixation on serum + urine; disappearance of soft tissue plasmacytomas; \<5 % plasma cells in bone marrow.
Time frame: From date of randomization until first documentation of CR, VGPR or PR (Up to approximately 3 years)
Population: ITT Population included all participants who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pomalidomide 4 mg + Dexamethasone 40 mg | Percentage of Participants With Overall Response | 41 percentage of participants |
| Ixazomib 4 mg + Dexamethasone 20 mg | Percentage of Participants With Overall Response | 38 percentage of participants |
p-value: =0.63495% CI: [0.43, 1.9]Cochran-Mantel-Haenszel
Secondary
Time to Progression (TTP)
TTP was defined as the time from the date of randomization to first documentation of PD. Per IMWG criteria, PD required 1 of the following: Increase of \>=25% from nadir in: Serum M-component (increase must be \>=0.5 g/dl; Urine M-component (increase must be \>=200 mg/24-hour); In participants without measurable serum and urine M-protein levels difference between involved and uninvolved FLC levels increase of \>10 mg/dl; In participants without measurable serum and urine M protein levels and without measurable disease by FLC level: Bone marrow plasma cell percentage must be \>=10%; Development of new or increase in size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (\>11.5 mg/dL corrected serum calcium) attributed solely to plasma cell proliferative disease.
Time frame: From date of randomization until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years)
Population: ITT Population included all participants who were randomized. Participants without documentation of PD at the time of analysis are censored at the date of last response assessment that is SD or better.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pomalidomide 4 mg + Dexamethasone 40 mg | Time to Progression (TTP) | 5.1 months |
| Ixazomib 4 mg + Dexamethasone 20 mg | Time to Progression (TTP) | 8.4 months |
p-value: =0.45995% CI: [0.506, 1.361]Log Rank
Secondary
Time to Response
Time to response was defined as the time from randomization to the first documentation of PR/VGPR/CR. Per IMWG criteria, PR: \>=50% reduction of serum M protein + reduction in 24-hour urinary M protein by \>=90% or to \<200 mg/24-hour; if M-protein is not measurable, \>=50% decrease in difference between involved and uninvolved FLC levels is required; if not measurable by FLC, \>=50% reduction in bone marrow plasma cells, when Baseline value \>=30% and; if present at Baseline, \>=50% reduction in size of soft tissue plasmacytomas is required. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein + urine M-protein level \<100 mg/24-hour. CR: negative immunofixation on serum + urine; disappearance of soft tissue plasmacytomas; \<5% plasma cells in bone marrow.
Time frame: From date of randomization until first documentation of CR, VGPR or PR (Up to approximately 3 years)
Population: Response Evaluable Population included all participants with multiple myeloma who had documentation of a confirmed PR, or PR/VGPR/CR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pomalidomide 4 mg + Dexamethasone 40 mg | Time to Response | 1.1 months |
| Ixazomib 4 mg + Dexamethasone 20 mg | Time to Response | 2.0 months |
95% CI: [0.288, 1.073]