A Study in Relapsed and/or Refractory Multiple Myeloma Patients Treated With Ixazomib Plus Lenalidomide and Dexamethasone

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• Multiple Myeloma 3,627
• Neoplasms, Plasma Cell 2,308

Study population

Groups and cohorts

• Ixazomib + Lenalidomide + Dexamethasone

  Participants took ixazomib, lenalidomide, and dexamethasone under conditions of standard medical care in this study. The dosage and administration of ixazomib, lenalidomide, and dexamethasone were not defined by the protocol but according to the package insert of each drug.

  Drug: Ixazomib · Drug: Lenalidomide · Drug: Dexamethasone

Interventions

• DrugIxazomib

  Ixazomib capsules

• DrugLenalidomide

  Lenalidomide capsules

• DrugDexamethasone

  Dexamethasone tablets

Primary outcomes

1. Progression-Free Survival (PFS)

   PFS was defined as the period from the start of ixazomib, lenalidomide, dexamethasone (IRd) therapy in standard medical care to the time of confirmed progressive disease (PD) or confirmed death (regardless of the cause of death), whichever was earlier. PFS was assessed by International Myeloma Working Group (IMWG) Criteria (2014 version). Per IMWG criteria, 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 36 Months as a maximum

Secondary outcomes

1. PFS Rate at 12 Months and 24 Months After the Start of Treatment

   PFS rate was defined as the percentage of participants who were alive and have not had disease progression at 12 months and 24 months after the date of start of study treatment. PFS was assessed by IMWG Criteria (2014 version). Per IMWG criteria, 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: 12 months and 24 months

2. Overall Survival (OS)

   OS is defined as the period from the start of IRd therapy in standard medical care to the time when death (regardless of the cause of death) is confirmed.

   Time frame: Up to 36 months as a maximum

3. 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 partial response (PR), very good PR (VGPR) and complete response (CR) assessed with IMWG Criteria after each cycle of treatment. 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 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: 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.

   Time frame: Up to 36 months as a maximum

4. Time to Next Treatment (TTNT)

   TTNT will be measured as the period from the start of IRd therapy in standard medical care to the start of next treatment or time when death is confirmed (regardless of the cause of death), whichever is earlier.

   Time frame: Up to 36 months as a maximum

5. Duration of Therapy (DOT)

   DOT is defined as the treatment duration of IRd therapy.

   Time frame: Up to 36 months as a maximum

6. Percentage of Participants Who Continue to Receive Treatment at 12 Months and 24 Months After Start of Treatment

   Time frame: 12 months and 24 months

7. 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.

   Time frame: Up to 36 months as a maximum

8. Percentage of Participants Who Achieve VGPR or Better (CR+VGPR)

   The percentage of participants of CR + VGPR is defined as the rate of participants who achieve a best response of VGPR or better (sCR, CR, or VGPR) according to the IMWG Criteria after the start of the IRd therapy.

   Time frame: Up to 36 months as a maximum

9. Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Global Health Status Score

   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. 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 of Global Health Status in EORTC QLQ-C30 were linearly transformed to a total score between 0-100 and reported, with a high score indicating better QOL.

   Time frame: Baseline and End of Treatment (Up to 37 cycles, each cycle was of 28 days)

10. 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 future perspective scale, higher score = better perspective of the future. For the body image scale, higher scores = better body image. Higher score for the disease symptoms scale = higher level of symptomatology.

    Time frame: Baseline and End of Treatment (Up to 37 cycles, each cycle was of 28 days)

11. Rate of Minimal Residual Disease (MRD) Negativity in Bone Marrow in Participants Who Achieved CR

    Rate of MRD will be calculated by the percentage of participants who are MRD-negative.

    Time frame: Up to 36 months as a maximum

12. Relative Dose Intensity (RDI)

    RDI 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 36 months as a maximum

13. Percentage of Participants With Bone Lesions (Bone Evaluation)

    Time frame: Up to 36 months as a maximum

14. 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 36 months as a maximum

Baseline characteristics

3 further baseline measures are reported on the registry.

Related links

• To obtain more information on the study, click here/on this link ↗

Study documents

• Study protocol · Aug 24, 2021
• Statistical analysis plan · Nov 1, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Supporting information: Study protocol, Sap, Icf, Csr