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

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

Population: Full Analysis Set, defined as all participants who were enrolled into the study and who receive at least one dose of ixazomib.

DOT is defined as the treatment duration of IRd therapy.

Time frame: Up to 36 months as a maximum

Population: Full Analysis Set, defined as all participants who were enrolled into the study and who receive at least one dose of ixazomib.

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

Population: Safety Analysis Set: all participants who were enrolled into the study and who receive at least one dose of any drug used in IRd therapy (i.e. ixazomib, lenalidomide, or dexamethasone)

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

Population: Full Analysis Set, defined as all participants who were enrolled into the study and who receive at least one dose of ixazomib.

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

Population: Full Analysis Set, defined as all participants who were enrolled into the study and who receive at least one dose of ixazomib.

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)

Population: Full Analysis Set, defined as all participants who were enrolled into the study and who receive at least one dose of ixazomib.

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)

Population: Full Analysis Set, defined as all participants who were enrolled into the study and who receive at least one dose of ixazomib.

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

Population: Full Analysis Set, defined as all participants who were enrolled into the study and who receive at least one dose of ixazomib.

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

Population: Full Analysis Set, defined as all participants who were enrolled into the study and who receive at least one dose of ixazomib.

Time frame: 12 months and 24 months

Population: Full Analysis Set, defined as all participants who were enrolled into the study and who receive at least one dose of ixazomib.

Time frame: Up to 36 months as a maximum

Population: Full Analysis Set, defined as all participants who were enrolled into the study and who receive at least one dose of ixazomib.

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

Population: Full Analysis Set, defined as all participants who were enrolled into the study and who receive at least one dose of ixazomib.

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

Time frame: Up to 36 months as a maximum

Population: Full Analysis Set, defined as all participants who were enrolled into the study and who receive at least one dose of ixazomib.

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

Population: Full Analysis Set, defined as all participants who were enrolled into the study and who receive at least one dose of ixazomib.

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

Population: Full Analysis Set, defined as all participants who were enrolled into the study and who receive at least one dose of ixazomib.