IXAZOMIB Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Newly Diagnosed Multiple Myeloma

Overall Response Rate (ORR)

ORR was defined as the percentage of participants who achieved CR + partial response (PR) + very good partial response (VGPR) (including sCR) or better relative to the ITT population during treatment period. CR was defined as negative immunofixation of serum and urine along with the disappearance of any soft tissue plasmacytomas and \<5 % PC's in bone marrow. PR was defined as ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% along with ≥50% reduction in the size of soft tissue plasmacytomas. VGPR was defined as ≥90% in serum M-component plus urine M-component \<100 mg/24. sCR is defined as stringent complete response. Percentages are rounded off to nearest whole numbers.

Time frame: Up to approximately 9 years

Time to Response

Time to response was defined as the time from the date of randomization to the first documentation of PR or better, as measured by IMWG criteria.

Time frame: Up to approximately 9 years

Duration of Response

Duration of response was measured as the time from the date of first documentation of PR or better to the date of first documented progression (PD) for responders, as measured by IMWG criteria.

Time frame: Up to approximately 9 years

Time to Progression (TTP)

Time to progression was defined as the time from randomization to the date of first documented disease progression.

Time frame: Up to approximately 9 years

Progression Free Survival (PFS)-2

PFS2 was defined as the time from the date of randomization to the date of documentation of disease progression on the subsequent line of anticancer therapy, as assessed by the investigator in accordance with IMWG criteria, or death due to any cause, whichever occurs first.

Time frame: Up to approximately 9 years

Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score

Eastern Cooperative Oncology Group (ECOG) scale score ranged from 0 to 5, where 0 indicated normal activity and 5 indicated death. The data is reported for those categories where at least 1 participant had worst post-baseline value for each ECOG score.

Time frame: Up to approximately 9 years

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

An AE was any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent.

Time frame: From the date of randomization through 30 days after the last dose of study drug up to end of study (up to approximately 9 years)

Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs)

The laboratory values assessment included serum chemistry and hematology. The Serum chemistry assessment included blood urea nitrogen (BUN), creatinine, bilirubin (total), urate, lactate dehydrogenase, phosphate, albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glucose, sodium, potassium, calcium, chloride, carbon dioxide (CO2), magnesium, thyroid stimulating hormone (TSH). Hematology assessment included hemoglobin, hematocrit, platelet (count), leukocytes with differential neutrophils (ANC). Participants with abnormal serum chemistry laboratory values reported as TEAEs are reported. TEAEs were defined as events that occurred after administration of the first dose of any agent in the study drug regimen and through 30 days after the last dose of any agent in the study drug regimen.

Time frame: From the date of randomization through 30 days after the last dose of study drug up to end of study (up to approximately 9 years)

Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score

EORTC-QLQ-C30 scale was used to assess HRQOL in cancer participants and contains 30 items. Subscale with individual items include physical functioning items 1-5, role functioning items 6-7, emotional functioning items 21-24, cognitive functioning items 20, 25, social functioning items 26-27, quality of life items 29-30, fatigue items 10, 12, 18, nausea and vomiting items 14-15, pain items 9, 19, dyspnoea item 8, insomnia item 11, appetite loss item 13, constipation item 16, diarrhoea item 17, financial difficulties item 28. Raw scores were converted into scale scores ranging from 0 to 100. For the functional scales and the global health status scale, higher scores represent better HRQOL; whereas for the symptom scales lower scores represent better HRQOL. Positive change in functional and global health status scale indicated improvement; negative change for the symptom scales indicates improvement.

Time frame: Baseline to approximately 9 years

Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale

EORTC QLQ-MY20 was a validated questionnaire to assess the overall quality of life in participants with multiple myeloma. The scale has 20 questions. Subscale and individual items include future perspective items 18-20, body image item 17, disease symptoms items 1-6, side effects of treatment items 7-16. Raw scores are averaged, and transformed to 0-100 scale, where higher score is better quality of life. Positive change indicates improvement.

Time frame: Baseline to approximately 9 years

OS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations

OS was defined as the time from the date of randomization to the date of death, as assessed in high-risk population carrying del(17p), t(4;14), or t(14;16) mutations. High risk category includes t(4;14), t(14;16), or del(17) abnormalities.

Time frame: From the date of randomization to death due to any cause (Up to approximately 9 years)

PFS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations

PFS was defined as the time from the date of randomization to the date of first documentation of progressive disease based on central laboratory results and IMWG criteria as evaluated by an independent review committee (IRC) or death due to any cause, whichever occurs first, as assessed in high-risk population carrying del(17p), t(4;14), or t(14;16) mutations.

Time frame: Up to approximately 9 years

Percentage of Participants With MRD-Negative Status as Assessed by Flow Cytometry

The absence of minimal residual disease (MRD negativity) was tested in all participants who achieve a CR and maintained it until Cycle 18, using bone marrow aspirates.

Time frame: Up to Cycle 18 (cycle length = 28 days)

Time to Pain Progression

Time to pain progression was assessed as the time from randomization to the date of initial progression classification. Pain progression was defined as the occurrence of 1 of the following and confirmed by 2 consecutive evaluations (To qualify as progression, the participant must have a BPI-SF worst pain score \> 4 during pain progression): 1) a ≥ 2 point and 30% increase from Baseline in BPI-SF worst pain score without an increase in analgesic use, or 2) a 25% or more increase in analgesic use from Baseline without a decrease in BPI-SF worst pain score from Baseline. Brief Pain Inventory - Short Form (m-BPI-SF) is a participant rated 11-point Likert rating scale ranged from 0 (no pain) to 10 (worst pain imaginable).

Time frame: Up to approximately 9 years

Cmax: Maximum Plasma Concentration for Ixazomib

Time frame: Cycle 1 Day 1: Post-dose at multiple timepoints up to 4 hours; Pre-dose at Cycle 1 Day 14, Cycles 2-3 Day 1 and Day 14, Cycles 4-11 Day 1 (Each cycle length = 28 days)

Percentage of Participants With New or Worsening of Existing Skeletal-related Events (SREs)

SRE is defined as new fractures \[including vertebral compression fractures\], irradiation of or surgery on bone, or spinal cord compression.

Time frame: From the date of randomization through 30 days after the last dose of study drug up to end of study (up to approximately 9 years)