A Study to Evaluate the Efficacy and Safety of Daratumumab in Combination With Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to CyBorD Alone in Newly Diagnosed Systemic Amyloid Light-chain (AL) Amyloidosis

Overall CHR rate was defined as percentage of participants who achieved CHR, according to the International Amyloidosis Consensus Criteria. CHR: normalization of free light chain levels and ratio, negative serum, and urine immunofixation. If involved free light chain (iFLC) is less than (<) upper limit of normal (ULN) and serum and urine Immunofixation electrophoresis (IFE) are negative, then neither a normal uninvolved free light chain (uFLC) level nor a normal free light chain (FLC) ratio are required for complete response (CR).

MOD-PFS was defined as duration from the date of randomization to either hematologic progression, or major organ deterioration (clinical manifestation of cardiac failure or renal failure), or death, whichever occurred first. Per international amyloidosis consensus criteria (IACC), hematologic progression was defined as satisfying any one of the following criteria: 1) From CHR, abnormal free light chain ratio (light chain must be double and >ULN); 2) From CHR/VGPR/PR, 50 percent (%) increase in serum M-protein to >0.5 grams per deciliter (g/dL) or 50% increase in urine M-protein to 200 milligrams (mg)/day; 3) free light chain increase of 50% to 100 milligrams (mg)/Liter (L).

Overall survival (OS) was measured from the date of randomization to the date of the participant's death.

The Organ Response Rate (OrRR) for heart was defined as the percentage of participants with baseline involvement of the heart who achieved a confirmed organ response in the heart. Cardiac response was defined as as a decrease of >30% in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and greater than (>)300 nanogram/Litre (ng/L).

The OrRR for kidney was defined as the percentage of participants with baseline involvement of the kidney who achieved a confirmed renal response in the kidney. Renal response was defined as more than equal to (≥) 30% decrease in proteinuria or proteinuria decreased to <0.5 grams (g)/24 hours in the absence of renal progression.

The OrRR for liver was defined as the percentage of participants with baseline involvement of the liver who achieved a confirmed liver response in the liver. Liver response was defined as 50% decrease in abnormal alkaline phosphatase value.

CHR rate was defined as percentage of participants who achieved CHR, according to the International Amyloidosis Consensus Criteria. CHR: normalization of free light chain levels and ratio, negative serum, and urine immunofixation. If involved free light chain is < ULN and serum and urine IFE are negative, then neither a normal uninvolved free light chain (uFLC) level nor a normal free light chain (FLC) ratio are required for Complete Response (CR).

Time to CHR was defined as time between the date of randomization and first efficacy evaluation at which the participant has met all criteria for hematologic CR. CHR was primarily defined by negative immunofixation results and normalized free light chain (FLC) parameters.

Time to cardiac response was defined as the time between the date of randomization and the first efficacy evaluation at which the participant had cardiac response.

Time to liver response was defined as the time between the date of randomization and the first efficacy evaluation at which the participant had liver response.

Time to renal response was defined as the time between the date of randomization and the first efficacy evaluation at which the participant had renal response.

Time to subsequent non-cross resistant anti-plasma cell therapy was defined as the time from the date of randomization to the start date of subsequent non-cross resistant, anti-plasma cell therapy.

Duration of CHR was defined as the time between the date of initial documentation of CHR to the date of first documented evidence of hematologic progressive diseased. CHR was primarily defined by negative immunofixation results and normalized FLC parameters.

Hematologic VGPR or Better Rate was defined as percentage of participants who achieved hematologic Complete response (CR) or VGPR. VGPR was defined as the difference between involved iFLC and uFLC after treatment for baseline difference between iFLC and uFLC (dFLC) >50 milligrams per liter (mg/L): Reduction in the dFLC <40 mg/L. For Baseline dFLC < 50 mg/L: more than (>) 90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours. CR was negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and < 5% PCs in bone marrow.

The EORTC-QLQ-C30 a 30-question tool was used to assess the overall quality of life (QoL) in cancer patients. It included 30 items resulting in 5 functional scales (physical, role, emotional, cognitive, and social functioning), 1 Global health status (GHS) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The questionnaire includes 28 items with 4-point Likert type responses from "1-not at all" to "4-very much" to assess functioning and symptoms; 2 items with 7-point Likert scales (1= poor and 7= excellent) for global health and overall QoL. Scores were transformed to a 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms.

The SF-36 Health Survey was a generic measure of health status. The SF-36 consisted of 36 questions that yield an eight-scale (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) profile of functional health and well-being, as well as 2 physical and mental health summary measures and a preference-based health utility index. The physical component summary (PCS), the mental component summary (MCS), and the 8 domain scores range from zero (0) to 100, with higher scores representing higher level of functioning.

The EORTC-QLQ-C30 a 30-question tool was used to assess the overall QoL in cancer patients. It included 30 items resulting in 5 functional scales (physical, role, emotional, cognitive, and social functioning), 1 GHS scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The questionnaire includes 28 items with 4-point Likert type responses from "1-not at all" to "4-very much" to assess functioning and symptoms; 2 items with 7-point Likert scales (1= poor and 7= excellent) for global health and overall QoL. Scores were transformed to a 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms.