Relapsed and/or Refractory Multiple Myeloma
Conditions
Brief summary
The purpose of this study is to investigate the efficacy and safety of long-term administration of the oral proteasome inhibitor ixazomib as part of ixazomib in combination with lenalidomide and dexamethasone (IRd) therapy in patients with relapsed and/or refractory multiple myeloma (RRMM) treated initially with an injectable proteasome inhibitor-based therapy.
Detailed description
The drug being tested in this study is called Ixazomib. Ixazomib is being tested to treat people who have RRMM. This study will look at the effectiveness and safety of IRd in participants with RRMM previously receiving an injectable proteasome inhibitor-based therapy. This study consists of two treatment periods, Treatment Period I and Treatment Period II. The study will enroll 47 patients. All participants will receive following treatment: \- Combination therapy with Bortezomib + Lenalidomide + Dexamethasone (VRd) or combination therapy with Carfilzomib + Lenalidomide + Dexamethasone (KRd), standard recommended dose according to the package insert of each drug, as Treatment Period I, followed by Combination therapy with Ixazomib 4.0 mg + Lenalidomide 25 mg + Dexamethasone 40 mg (IRd) as Treatment Period II At start of this study, combination therapy of VRd or KRd will be decided by investigator as Treatment Period I after the baseline evaluations. After the start of Treatment Period I, a participant's eligibility for Treatment Period II is then determined 3 cycles. Participants who meet these eligibility criteria II subsequently continue into Treatment Period II and receive IRd. This multi-center trial will be conducted in Japan. It is anticipated that the treatment phase of this study will last up to 39 months, including 18 months for enrollment. Participants will make multiple visits to the clinic in treatment period, and follow-up period including a follow-up assessment after last dose of study drug.
Interventions
DRUGIxazomib
Ixazomib capsules
DRUGBortezomib
Bortezomib injections
DRUGCarfilzomib
Carfilzomib intravenous infusions
DRUGLenalidomide
Lenalidomide capsules
DRUGDexamethasone
Dexamethasone tablets
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Eligibility for Treatment Period I 1. Men and women of age 20 years or older at the time of enrollment. 2. Participants with RRMM. 3. Participants who are planned to start combination therapy with bortezomib, lenalidomide, and dexamethasone (VRd) or carfilzomib, lenalidomide, and dexamethasone (KRd) as second, third or fourth line of treatment. 4. Participants with measurable disease defined by one or more of the following three measurements. * Serum M-protein: ≥0.5 gram (g)/ deciliter (dL) (≥ 5 g/ liter \[L\]) * Urine M-protein: ≥ 200 milligram (mg)/24 hours * Serum free light chain assay: involved free light chain concentration ≥ 10 mg/dL (≥ 100 mg/L) provided that the serum free light chain ratio is abnormal 5. Participants with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2; however, participants with ECOG PS 3 are eligible if they only have symptoms associated with bone lesions. 6. Participants who are considered by the principal investigator or investigator not to be eligible for transplant; or, if considered eligible for transplant, participants who are planned not to undergo transplant for at least 12 months after the start of the study treatment. 7. Participants must be registered with, and comply with, the guidelines of the lenalidomide management program. 8. Participants who, before implementing procedures related to clinical research (excluding standard medical practices), understand that they can withdraw consent at any time without suffering from disadvantages to future treatments, and can provide written informed consent. Eligibility for Treatment Period II 9. Participants must have received an injectable proteasome inhibitor (bortezomib or carfilzomib) in each treatment cycle of Treatment Period I.
Exclusion criteria
Eligibility for Treatment Period I 1. Women who are nursing or pregnant. 2. Participants with another active malignancy, i.e. synchronous active malignancy or previous malignancy with a disease-free period of less than 5 years, except for participants with carcinoma in situ (intraepithelial carcinoma) or intramucosal carcinoma judged to be cured by topical treatment. 3. Participants with poorly controlled active thrombosis. 4. Participants who have participated in a clinical trial of ixazomib or have been treated with ixazomib. 5. Participants who were refractory to either treatment regimen based on lenalidomide and/or proteasome inhibitor(s). Note: Refractory MM is defined as PD on therapy or PD within 60 days after the last dose of a given therapy. Participants who have disease progressed 60 days after the last dose of a given therapy will be considered as relapsed in this study. 6. Participants with ongoing or active systemic infection, known hepatitis B virus infection, known hepatitis C virus infection, or known positivity to human immunodeficiency virus (HIV). 7. Participants who underwent major surgery within 14 days prior to enrollment to Treatment Period I. Surgery for bone lesions is not considered as major surgery. 8. Participants who received radiation therapy within 14 days prior to enrollment to Treatment Period I. If the radiation field is small, 7 days is considered as a sufficient interval between radiation therapy and chemotherapy. 9. Participants who experience Grade 1 peripheral neuropathy accompanied by pain, or Grade ≥2 peripheral neuropathy. 10. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmia, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months before enrollment to Treatment Period I. 11. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before enrollment into Treatment Period I. 12. Participants with central nervous system involvement. 13. Inability to swallow oral medications, inability or unwillingness to comply with the drug administration requirements, or gastrointestinal conditions that could interfere with the oral absorption or tolerance of treatment. 14. Psychiatric illness/social situation that would limit compliance with study requirements. 15. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens. Eligibility for Treatment Period II 16. Participants who do not achieve at least a minimal response (MR) to VRd or KRd in Treatment Period I per the International Myeloma Working Group (IMWG) response criteria, 2014 revision. 17. Participants who experience Grade 1 peripheral neuropathy accompanied by pain, or Grade ≥2 peripheral neuropathy during Treatment Period I. 18. Participants with evidence of uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmia, symptomatic congestive heart failure, unstable angina, or myocardial infarction during Treatment Period I. 19. Participants using potent CYP3A4 inducing agents (rifampicin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or gingko biloba or St. John's wort. 20. Participants with hypersensitivity to any of the IRd study medications, their analogs, or excipients contained in IRd. 21. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) Rate at 12 Months From the Start of Study Treatment | Up to 12 months | PFS rate was defined as the percentage of participants who were alive and have not had disease progression at 12 months after the date of first dose of treatment in Treatment Period I. PFS was assessed by International Myeloma Working Group (IMWG) Criteria (2014 version). Per IMWG criteria, progressive disease (PD): serum M-component increase ≥0.5 g/dl or urine M-component increase ≥200 mg/24-hour/ difference between involved and uninvolved free light chain (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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS From the Start of Study Treatment | Up to 39 months as a maximum | PFS was defined as the period from the first dose of treatment in Treatment Period I to the time of confirmed PD or confirmed death (regardless of the cause of death), whichever is earlier. PFS was assessed by IMWG Criteria. |
| Percentage of Participants Who Achieved VGPR or Better (CR + VGPR) | Up to 39 months as a maximum | VGPR or better (CR + VGPR) were assessed by IMWG Criteria. Per IMWG criteria, PR (partial response): ≥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 free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level \<100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow. |
| Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR | Up to 39 months as a maximum | MRD was measured by the flow cytometry method using bone marrow aspiration. Reported data were numbers of participants with MRD positive and negative in bone marrow in participants who achieved CR. MRD positive was categorized into three sensitivity levels with the numbers of cells counted (10\^-4 to - Max; 10\^-5 to 10\^-4; 10\^-6 to 10\^-5). MRD negativity is defined as absence of MRD and MRD positivity is defined as presence of MRD. If a participant is MRD-positive at their first evaluation and MRD-negative after re-examination, the participant will be considered to be MRD-negative. CR will be assessed by IMWG Criteria. |
| Percentage of Participants Who Achieve or Maintain Any Best Response | Up to 39 months as a maximum | Best response is defined as the cumulative numbers of participants who achieve each level of best response including PR, VGPR and CR assessed with IMWG Criteria, after each cycle of treatment. Per IMWG criteria, PR (partial response): ≥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 free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level \<100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow. |
| Overall Response Rate (ORR) | Up to 39 months as a maximum | ORR is defined as the percentage of participants who achieve a best response of PR or better including stringent complete response (sCR), VGPR and PR assessed with IMWG Criteria, after the start of the study treatment. Per IMWG criteria, PR (partial response): ≥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 free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level \<100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow. |
| Percentage of Participants Continuing Treatment With Ixazomib at 12 Months From the Start of Study Treatment | 12 months | — |
| Duration of Response (DOR) | Up to 39 months as a maximum | DOR is defined as the time from the date of first documentation of response ≥PR to the date of first documentation of PD or death due to any cause. PR and PD will be assessed with IMWG Criteria. Per IMWG criteria, PR (partial response): ≥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 free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level \<100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow. |
| Time to Next Treatment (TTNT) | Up to 39 months as a maximum | TTNT is defined as the period from the start of study treatment Period I to the start of next line treatment. |
| Overall Survival (OS) From the Start of Study Treatment | Up to 39 months as a maximum | OS was defined as the period from the first dose of treatment in Treatment Period I to the time when death (regardless of the cause of death) was confirmed. Participants who were still alive were censored at the last confirmed date of survival or the date of data cut-off, whichever was earlier. |
| Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on Global Health Status Scale of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Baseline and End of Treatment (Up to 23 cycles for VRd Group, Up to 32 cycles for KRd and Overall Group, each cycle was of 28 days) | 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/QOL scale (Global Health Status). EORTC QLQ-C30 contains 28 questions (4-point scale where 1=Not at all \[best\] to 4=Very Much \[worst\]) and 2 questions (7-point scale where 1=Very poor \[worst\] to 7= Excellent \[best\]). Raw scores are converted into scale scores ranging from 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. |
| Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Baseline and End of Treatment (Up to 23 cycles for VRd Group, Up to 32 cycles for KRd and Overall Group, each cycle was of 28 days) | EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 functional subscales (body image, future perspective), and 2 symptoms scales (disease symptoms, and side effects of treatment). Scores are averaged, and transformed to 0-100 scale. For the functional scales, high scores represent improvement. For the symptom scales, higher scores represent worsening. |
| Evaluation of Modified Quality-Adjusted Life-Years (QALYs) | Up to 39 months as a maximum | Modified QALYs was calculated from the score of EORTC QLQ-C30. The health-related quality of life scale score of EORTC QLQ-C30 was converted into a utility value ranging from 0 (dead) to 1 (perfect health), and used to adjust the value of survival years; this value was assessed as the modified QALY. |
| Healthcare Resource Utilization (HCRU): Number of Events With Hospitalization Per Participants-Month | Up to 39 months as a maximum | HCRU was calculated from Exposure-adjusted rate of hospitalization events (per participants-months) and the duration of hospitalization among participants in Treatment Period I and Treatment Period II. Number of events with hospitalization per participants-month in Treatment Period I and Treatment Period II was reported. |
| Healthcare Resource Utilization (HCRU): Duration of Hospital Stay Per Participants | Up to 39 months as a maximum | HCRU was calculated from Exposure-adjusted rate of hospitalization events (per participants-months) and the duration of hospitalization among participants in Treatment Period I and Treatment Period II. Duration of hospital stay per participants in Treatment Period I and Treatment Period II was reported. |
| Relative Dose Intensity (RDI) | Up to 39 months as a maximum | RDI for each study drug is defined as 100\*(Total amount of dose taken)/(Total prescribed dose of treated cycles), where total prescribed dose equals \[dose prescribed at enrollment\* number of prescribed doses per cycle\* the number of treated cycles\]. |
| Percentage of Participants With Bone Lesions (Bone Evaluation) | Up to 39 months as a maximum | — |
| Number of Participants Reporting One or More Treatment-Emergent AEs (TEAEs) | Up to 39 months as a maximum | An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. |
| Duration of Therapy (DOT) | Up to 39 months as a maximum | DOT is defined as the treatment duration of study drug at study treatment Period I. |
Countries
Japan
Participant flow
Recruitment details
Participant s took part in the survey at 33 investigative sites in Japan, from 18 February 2018 to 28 May 2021.
Pre-assignment details
A total of 45 participants were enrolled and received the study treatment in this study.
Participants by arm
| Arm | Count |
|---|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II) | 6 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II) | 39 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Between Treatment Period I and II | Other | 0 | 9 |
| Treatment Period II | Adverse Event | 1 | 4 |
| Treatment Period II | Death | 0 | 1 |
| Treatment Period II | Lack of Efficacy | 3 | 11 |
| Treatment Period II | Other | 0 | 2 |
Baseline characteristics
| Characteristic | [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Total | [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy |
|---|---|---|---|
| Age, Continuous | 70.5 Years STANDARD_DEVIATION 9.4 | 70.7 Years STANDARD_DEVIATION 9.21 | 71.8 Years STANDARD_DEVIATION 8.57 |
| BMI | 22.91 Kilogram (kg)/meter (m)^2] STANDARD_DEVIATION 2.512 | 22.86 Kilogram (kg)/meter (m)^2] STANDARD_DEVIATION 2.497 | 22.60 Kilogram (kg)/meter (m)^2] STANDARD_DEVIATION 2.619 |
| Body Surface Area | 1.583 m^2 STANDARD_DEVIATION 0.176 | 1.569 m^2 STANDARD_DEVIATION 0.1732 | 1.487 m^2 STANDARD_DEVIATION 0.1395 |
| Eastern Cooperative Oncology Group performance status (ECOG P.S.) Scale = 0 | 29 Participants | 33 Participants | 4 Participants |
| Eastern Cooperative Oncology Group performance status (ECOG P.S.) Scale = 1 | 8 Participants | 10 Participants | 2 Participants |
| Eastern Cooperative Oncology Group performance status (ECOG P.S.) Scale = 2 | 2 Participants | 2 Participants | 0 Participants |
| Eastern Cooperative Oncology Group performance status (ECOG P.S.) Scale = 3 | 0 Participants | 0 Participants | 0 Participants |
| Eastern Cooperative Oncology Group performance status (ECOG P.S.) Scale = 4 | 0 Participants | 0 Participants | 0 Participants |
| Height | 158.5 Centimeters (cm) STANDARD_DEVIATION 8.29 | 157.8 Centimeters (cm) STANDARD_DEVIATION 8.58 | 153.0 Centimeters (cm) STANDARD_DEVIATION 9.7 |
| International Staging System (at First Treatment [Period I]) Missing | 3 Participants | 3 Participants | 0 Participants |
| International Staging System (at First Treatment [Period I]) Stage I | 19 Participants | 24 Participants | 5 Participants |
| International Staging System (at First Treatment [Period I]) Stage II | 12 Participants | 13 Participants | 1 Participants |
| International Staging System (at First Treatment [Period I]) Stage III | 5 Participants | 5 Participants | 0 Participants |
| International Staging System (at Initial Diagnosis) Stage I | 17 Participants | 19 Participants | 2 Participants |
| International Staging System (at Initial Diagnosis) Stage II | 14 Participants | 17 Participants | 3 Participants |
| International Staging System (at Initial Diagnosis) Stage III | 8 Participants | 9 Participants | 1 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Japan | 39 Participants | 45 Participants | 6 Participants |
| Sex: Female, Male Female | 16 Participants | 21 Participants | 5 Participants |
| Sex: Female, Male Male | 23 Participants | 24 Participants | 1 Participants |
| Weight | 57.87 Kilograms (kg) STANDARD_DEVIATION 10.38 | 57.17 Kilograms (kg) STANDARD_DEVIATION 10.081 | 52.85 Kilograms (kg) STANDARD_DEVIATION 7.204 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 2 / 39 | 2 / 45 |
| other Total, other adverse events | 6 / 6 | 31 / 39 | 37 / 45 |
| serious Total, serious adverse events | 3 / 6 | 14 / 39 | 17 / 45 |
Outcome results
Primary
Progression-Free Survival (PFS) Rate at 12 Months From the Start of Study Treatment
PFS rate was defined as the percentage of participants who were alive and have not had disease progression at 12 months after the date of first dose of treatment in Treatment Period I. PFS was assessed by International Myeloma Working Group (IMWG) Criteria (2014 version). Per IMWG criteria, progressive disease (PD): serum M-component increase ≥0.5 g/dl or urine M-component increase ≥200 mg/24-hour/ difference between involved and uninvolved free light chain (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: Up to 12 months
Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Progression-Free Survival (PFS) Rate at 12 Months From the Start of Study Treatment | 50.0 Percentage of Participants |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Progression-Free Survival (PFS) Rate at 12 Months From the Start of Study Treatment | 48.7 Percentage of Participants |
| [Overall]; Combination Therapy + Ixazomib Therapy | Progression-Free Survival (PFS) Rate at 12 Months From the Start of Study Treatment | 48.9 Percentage of Participants |
Secondary
Duration of Response (DOR)
DOR is defined as the time from the date of first documentation of response ≥PR to the date of first documentation of PD or death due to any cause. PR and PD will be assessed with IMWG Criteria. Per IMWG criteria, PR (partial response): ≥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 free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level \<100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow.
Time frame: Up to 39 months as a maximum
Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Duration of Response (DOR) | 15.31 Months |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Duration of Response (DOR) | 28.03 Months |
| [Overall]; Combination Therapy + Ixazomib Therapy | Duration of Response (DOR) | 28.03 Months |
Secondary
Duration of Therapy (DOT)
DOT is defined as the treatment duration of study drug at study treatment Period I.
Time frame: Up to 39 months as a maximum
Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Duration of Therapy (DOT) | 14.69 Months |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Duration of Therapy (DOT) | 12.43 Months |
| [Overall]; Combination Therapy + Ixazomib Therapy | Duration of Therapy (DOT) | 12.43 Months |
Secondary
Evaluation of Modified Quality-Adjusted Life-Years (QALYs)
Modified QALYs was calculated from the score of EORTC QLQ-C30. The health-related quality of life scale score of EORTC QLQ-C30 was converted into a utility value ranging from 0 (dead) to 1 (perfect health), and used to adjust the value of survival years; this value was assessed as the modified QALY.
Time frame: Up to 39 months as a maximum
Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Evaluation of Modified Quality-Adjusted Life-Years (QALYs) | 0.467 Quality-Adjusted Life-Years |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Evaluation of Modified Quality-Adjusted Life-Years (QALYs) | 0.534 Quality-Adjusted Life-Years |
| [Overall]; Combination Therapy + Ixazomib Therapy | Evaluation of Modified Quality-Adjusted Life-Years (QALYs) | 0.518 Quality-Adjusted Life-Years |
Secondary
Healthcare Resource Utilization (HCRU): Duration of Hospital Stay Per Participants
HCRU was calculated from Exposure-adjusted rate of hospitalization events (per participants-months) and the duration of hospitalization among participants in Treatment Period I and Treatment Period II. Duration of hospital stay per participants in Treatment Period I and Treatment Period II was reported.
Time frame: Up to 39 months as a maximum
Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Healthcare Resource Utilization (HCRU): Duration of Hospital Stay Per Participants | 14.8 Days | Standard Deviation 16.01 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Healthcare Resource Utilization (HCRU): Duration of Hospital Stay Per Participants | 19.4 Days | Standard Deviation 18.14 |
| [Overall]; Combination Therapy + Ixazomib Therapy | Healthcare Resource Utilization (HCRU): Duration of Hospital Stay Per Participants | 18.8 Days | Standard Deviation 17.77 |
Secondary
Healthcare Resource Utilization (HCRU): Number of Events With Hospitalization Per Participants-Month
HCRU was calculated from Exposure-adjusted rate of hospitalization events (per participants-months) and the duration of hospitalization among participants in Treatment Period I and Treatment Period II. Number of events with hospitalization per participants-month in Treatment Period I and Treatment Period II was reported.
Time frame: Up to 39 months as a maximum
Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Healthcare Resource Utilization (HCRU): Number of Events With Hospitalization Per Participants-Month | 1.9 Number of Events per Participants-Month |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Healthcare Resource Utilization (HCRU): Number of Events With Hospitalization Per Participants-Month | 2.9 Number of Events per Participants-Month |
| [Overall]; Combination Therapy + Ixazomib Therapy | Healthcare Resource Utilization (HCRU): Number of Events With Hospitalization Per Participants-Month | 2.7 Number of Events per Participants-Month |
Secondary
Number of Participants Reporting One or More Treatment-Emergent AEs (TEAEs)
An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: Up to 39 months as a maximum
Population: Safety Analysis Set: all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Number of Participants Reporting One or More Treatment-Emergent AEs (TEAEs) | 6 Participants |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Number of Participants Reporting One or More Treatment-Emergent AEs (TEAEs) | 35 Participants |
| [Overall]; Combination Therapy + Ixazomib Therapy | Number of Participants Reporting One or More Treatment-Emergent AEs (TEAEs) | 41 Participants |
Secondary
Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR
MRD was measured by the flow cytometry method using bone marrow aspiration. Reported data were numbers of participants with MRD positive and negative in bone marrow in participants who achieved CR. MRD positive was categorized into three sensitivity levels with the numbers of cells counted (10\^-4 to - Max; 10\^-5 to 10\^-4; 10\^-6 to 10\^-5). MRD negativity is defined as absence of MRD and MRD positivity is defined as presence of MRD. If a participant is MRD-positive at their first evaluation and MRD-negative after re-examination, the participant will be considered to be MRD-negative. CR will be assessed by IMWG Criteria.
Time frame: Up to 39 months as a maximum
Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR | Sensitivity Level; 10^-4=< - Max | 0 Participants |
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR | Sensitivity Level; 10^-5=< - <10^-4 | 1 Participants |
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR | Sensitivity Level; 10^-6=< - <10^-5 | 1 Participants |
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR | Negative | 0 Participants |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR | Negative | 5 Participants |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR | Sensitivity Level; 10^-4=< - Max | 1 Participants |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR | Sensitivity Level; 10^-6=< - <10^-5 | 1 Participants |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR | Sensitivity Level; 10^-5=< - <10^-4 | 2 Participants |
| [Overall]; Combination Therapy + Ixazomib Therapy | Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR | Negative | 5 Participants |
| [Overall]; Combination Therapy + Ixazomib Therapy | Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR | Sensitivity Level; 10^-5=< - <10^-4 | 3 Participants |
| [Overall]; Combination Therapy + Ixazomib Therapy | Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR | Sensitivity Level; 10^-6=< - <10^-5 | 2 Participants |
| [Overall]; Combination Therapy + Ixazomib Therapy | Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR | Sensitivity Level; 10^-4=< - Max | 1 Participants |
Secondary
Overall Response Rate (ORR)
ORR is defined as the percentage of participants who achieve a best response of PR or better including stringent complete response (sCR), VGPR and PR assessed with IMWG Criteria, after the start of the study treatment. Per IMWG criteria, PR (partial response): ≥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 free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level \<100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow.
Time frame: Up to 39 months as a maximum
Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Overall Response Rate (ORR) | 83.3 Percentage of Participants |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Overall Response Rate (ORR) | 71.8 Percentage of Participants |
| [Overall]; Combination Therapy + Ixazomib Therapy | Overall Response Rate (ORR) | 73.3 Percentage of Participants |
Secondary
Overall Survival (OS) From the Start of Study Treatment
OS was defined as the period from the first dose of treatment in Treatment Period I to the time when death (regardless of the cause of death) was confirmed. Participants who were still alive were censored at the last confirmed date of survival or the date of data cut-off, whichever was earlier.
Time frame: Up to 39 months as a maximum
Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Overall Survival (OS) From the Start of Study Treatment | NA Months |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Overall Survival (OS) From the Start of Study Treatment | NA Months |
| [Overall]; Combination Therapy + Ixazomib Therapy | Overall Survival (OS) From the Start of Study Treatment | NA Months |
Secondary
Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on Global Health Status Scale of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30)
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/QOL scale (Global Health Status). EORTC QLQ-C30 contains 28 questions (4-point scale where 1=Not at all \[best\] to 4=Very Much \[worst\]) and 2 questions (7-point scale where 1=Very poor \[worst\] to 7= Excellent \[best\]). Raw scores are converted into scale scores ranging from 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.
Time frame: Baseline and End of Treatment (Up to 23 cycles for VRd Group, Up to 32 cycles for KRd and Overall Group, each cycle was of 28 days)
Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on Global Health Status Scale of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Baseline | 44.44 Score on a Scale | Standard Deviation 40.369 |
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on Global Health Status Scale of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Cycle 23 | 0 Score on a Scale | — |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on Global Health Status Scale of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Cycle 23 | 54.17 Score on a Scale | Standard Deviation 8.74 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on Global Health Status Scale of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Baseline | 63.25 Score on a Scale | Standard Deviation 24.085 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on Global Health Status Scale of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Cycle 32 | 50.00 Score on a Scale | Standard Deviation 23.75 |
| [Overall]; Combination Therapy + Ixazomib Therapy | Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on Global Health Status Scale of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Cycle 23 | 46.43 Score on a Scale | Standard Deviation 21.973 |
| [Overall]; Combination Therapy + Ixazomib Therapy | Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on Global Health Status Scale of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Cycle 32 | 50.00 Score on a Scale | Standard Deviation 23.75 |
| [Overall]; Combination Therapy + Ixazomib Therapy | Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on Global Health Status Scale of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) | Baseline | 60.74 Score on a Scale | Standard Deviation 26.981 |
Secondary
Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score
EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 functional subscales (body image, future perspective), and 2 symptoms scales (disease symptoms, and side effects of treatment). Scores are averaged, and transformed to 0-100 scale. For the functional scales, high scores represent improvement. For the symptom scales, higher scores represent worsening.
Time frame: Baseline and End of Treatment (Up to 23 cycles for VRd Group, Up to 32 cycles for KRd and Overall Group, each cycle was of 28 days)
Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Disease Symptoms: Baseline | 24.07 Score on a Scale | Standard Deviation 21.564 |
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Disease Symptoms: Cycle 23 | 0 Score on a Scale | — |
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Side-Effects of Treatment: Baseline | 16.67 Score on a Scale | Standard Deviation 12.776 |
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Side-Effects of Treatment: Cycle 23 | 3.70 Score on a Scale | — |
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Body Image: Baseline | 44.44 Score on a Scale | Standard Deviation 45.542 |
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Body Image: Cycle 23 | 0 Score on a Scale | — |
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Future Perspective: Baseline | 66.67 Score on a Scale | Standard Deviation 37.185 |
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Future Perspective: Cycle 23 | 11.11 Score on a Scale | — |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Body Image: Cycle 23 | 16.67 Score on a Scale | Standard Deviation 18.257 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Side-Effects of Treatment: Cycle 23 | 16.05 Score on a Scale | Standard Deviation 3.825 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Body Image: Cycle 32 | 16.67 Score on a Scale | Standard Deviation 23.57 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Future Perspective: Cycle 23 | 35.19 Score on a Scale | Standard Deviation 8.364 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Future Perspective: Cycle 32 | 27.78 Score on a Scale | Standard Deviation 7.857 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Disease Symptoms: Baseline | 19.23 Score on a Scale | Standard Deviation 16.756 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Body Image: Baseline | 23.08 Score on a Scale | Standard Deviation 26.66 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Future Perspective: Baseline | 44.16 Score on a Scale | Standard Deviation 24.114 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Disease Symptoms: Cycle 23 | 4.63 Score on a Scale | Standard Deviation 7.384 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Side-Effects of Treatment: Baseline | 16.60 Score on a Scale | Standard Deviation 14.464 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Disease Symptoms: Cycle 32 | 2.78 Score on a Scale | Standard Deviation 3.928 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Side-Effects of Treatment: Cycle 32 | 18.52 Score on a Scale | Standard Deviation 15.713 |
| [Overall]; Combination Therapy + Ixazomib Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Disease Symptoms: Cycle 32 | 2.78 Score on a Scale | Standard Deviation 3.928 |
| [Overall]; Combination Therapy + Ixazomib Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Side-Effects of Treatment: Baseline | 16.61 Score on a Scale | Standard Deviation 14.115 |
| [Overall]; Combination Therapy + Ixazomib Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Future Perspective: Cycle 32 | 27.78 Score on a Scale | Standard Deviation 7.857 |
| [Overall]; Combination Therapy + Ixazomib Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Side-Effects of Treatment: Cycle 23 | 14.29 Score on a Scale | Standard Deviation 5.828 |
| [Overall]; Combination Therapy + Ixazomib Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Side-Effects of Treatment: Cycle 32 | 18.52 Score on a Scale | Standard Deviation 15.713 |
| [Overall]; Combination Therapy + Ixazomib Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Body Image: Baseline | 25.93 Score on a Scale | Standard Deviation 30.058 |
| [Overall]; Combination Therapy + Ixazomib Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Future Perspective: Cycle 23 | 31.75 Score on a Scale | Standard Deviation 11.878 |
| [Overall]; Combination Therapy + Ixazomib Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Body Image: Cycle 23 | 14.29 Score on a Scale | Standard Deviation 17.817 |
| [Overall]; Combination Therapy + Ixazomib Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Body Image: Cycle 32 | 16.67 Score on a Scale | Standard Deviation 23.57 |
| [Overall]; Combination Therapy + Ixazomib Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Disease Symptoms: Baseline | 19.88 Score on a Scale | Standard Deviation 17.266 |
| [Overall]; Combination Therapy + Ixazomib Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Disease Symptoms: Cycle 23 | 3.97 Score on a Scale | Standard Deviation 6.964 |
| [Overall]; Combination Therapy + Ixazomib Therapy | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score | Future Perspective: Baseline | 47.16 Score on a Scale | Standard Deviation 26.817 |
Secondary
Percentage of Participants Continuing Treatment With Ixazomib at 12 Months From the Start of Study Treatment
Time frame: 12 months
Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Percentage of Participants Continuing Treatment With Ixazomib at 12 Months From the Start of Study Treatment | 50.0 Percentage of Participants |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Percentage of Participants Continuing Treatment With Ixazomib at 12 Months From the Start of Study Treatment | 35.9 Percentage of Participants |
| [Overall]; Combination Therapy + Ixazomib Therapy | Percentage of Participants Continuing Treatment With Ixazomib at 12 Months From the Start of Study Treatment | 37.8 Percentage of Participants |
Secondary
Percentage of Participants Who Achieved VGPR or Better (CR + VGPR)
VGPR or better (CR + VGPR) were assessed by IMWG Criteria. Per IMWG criteria, PR (partial response): ≥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 free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level \<100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow.
Time frame: Up to 39 months as a maximum
Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Percentage of Participants Who Achieved VGPR or Better (CR + VGPR) | 33.3 Percentage of Participants |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Percentage of Participants Who Achieved VGPR or Better (CR + VGPR) | 43.6 Percentage of Participants |
| [Overall]; Combination Therapy + Ixazomib Therapy | Percentage of Participants Who Achieved VGPR or Better (CR + VGPR) | 42.2 Percentage of Participants |
Secondary
Percentage of Participants Who Achieve or Maintain Any Best Response
Best response is defined as the cumulative numbers of participants who achieve each level of best response including PR, VGPR and CR assessed with IMWG Criteria, after each cycle of treatment. Per IMWG criteria, PR (partial response): ≥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 free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level \<100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow.
Time frame: Up to 39 months as a maximum
Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Percentage of Participants Who Achieve or Maintain Any Best Response | VGPR | 0 Percentage of Participants |
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Percentage of Participants Who Achieve or Maintain Any Best Response | CR | 33.3 Percentage of Participants |
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Percentage of Participants Who Achieve or Maintain Any Best Response | PR | 50.0 Percentage of Participants |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Percentage of Participants Who Achieve or Maintain Any Best Response | VGPR | 20.5 Percentage of Participants |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Percentage of Participants Who Achieve or Maintain Any Best Response | CR | 23.1 Percentage of Participants |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Percentage of Participants Who Achieve or Maintain Any Best Response | PR | 28.2 Percentage of Participants |
| [Overall]; Combination Therapy + Ixazomib Therapy | Percentage of Participants Who Achieve or Maintain Any Best Response | CR | 24.4 Percentage of Participants |
| [Overall]; Combination Therapy + Ixazomib Therapy | Percentage of Participants Who Achieve or Maintain Any Best Response | PR | 31.1 Percentage of Participants |
| [Overall]; Combination Therapy + Ixazomib Therapy | Percentage of Participants Who Achieve or Maintain Any Best Response | VGPR | 17.8 Percentage of Participants |
Secondary
Percentage of Participants With Bone Lesions (Bone Evaluation)
Time frame: Up to 39 months as a maximum
Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Percentage of Participants With Bone Lesions (Bone Evaluation) | 100.0 Percentage of Participants |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Percentage of Participants With Bone Lesions (Bone Evaluation) | 59.1 Percentage of Participants |
| [Overall]; Combination Therapy + Ixazomib Therapy | Percentage of Participants With Bone Lesions (Bone Evaluation) | 64.0 Percentage of Participants |
Secondary
PFS From the Start of Study Treatment
PFS was defined as the period from the first dose of treatment in Treatment Period I to the time of confirmed PD or confirmed death (regardless of the cause of death), whichever is earlier. PFS was assessed by IMWG Criteria.
Time frame: Up to 39 months as a maximum
Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | PFS From the Start of Study Treatment | NA Months |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | PFS From the Start of Study Treatment | 28.96 Months |
| [Overall]; Combination Therapy + Ixazomib Therapy | PFS From the Start of Study Treatment | 28.96 Months |
Secondary
Relative Dose Intensity (RDI)
RDI for each study drug is defined as 100\*(Total amount of dose taken)/(Total prescribed dose of treated cycles), where total prescribed dose equals \[dose prescribed at enrollment\* number of prescribed doses per cycle\* the number of treated cycles\].
Time frame: Up to 39 months as a maximum
Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Relative Dose Intensity (RDI) | Bortezomib, Ixazomib | 71.93 Percent |
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Relative Dose Intensity (RDI) | Carfilzomib, Ixazomib | 87.70 Percent |
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Relative Dose Intensity (RDI) | Bortezomib/Carfilzomib, Ixazomib | 83.24 Percent |
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Relative Dose Intensity (RDI) | Lenalidomide | 47.18 Percent |
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Relative Dose Intensity (RDI) | Dexamethasone | 48.61 Percent |
Secondary
Time to Next Treatment (TTNT)
TTNT is defined as the period from the start of study treatment Period I to the start of next line treatment.
Time frame: Up to 39 months as a maximum
Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | Time to Next Treatment (TTNT) | 21.59 Months |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | Time to Next Treatment (TTNT) | 32.26 Months |
| [Overall]; Combination Therapy + Ixazomib Therapy | Time to Next Treatment (TTNT) | 32.26 Months |