Trial Outcomes & Findings for A Study to Evaluate 3 Dose Schedules of Daratumumab in Participants With Smoldering Multiple Myeloma (NCT NCT02316106)

A Study to Evaluate 3 Dose Schedules of Daratumumab in Participants With Smoldering Multiple Myeloma

Percentage of participants who achieved a CR by IMWG Criteria were reported. CR was defined as CR plus stringent complete Response (sCR) by IMWG criteria. Per IMWG criteria, CR response was defined as a negative immunofixation on the serum and urine, and less than (\<) 5 percentage (%) plasma cells in bone marrow; sCR was defined as CR plus normal free light chain (FLC) ratio, and absence of clonal plasma cells by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.

Progressive disease (PD) or death rate were reported. PD or death rate per patient-year was defined as number of events (PD or death) divided by total progression-free survival (PFS) for all participants.

MRD negative rate were reported. The MRD negativity rate was defined as the percentage of participants with a CR or better response who had negative MRD (10\^-4 and 10\^-5) assessment at any timepoint after the first dose of study drugs by evaluation of bone marrow aspirates at any time after the randomization and prior to progressive disease, subsequent therapy.

Time to next treatment (TNT) for active myeloma were reported. Time to next treatment was defined as the time from the date of randomization to the date of the first subsequent multiple myeloma treatment. Kaplan-Meier estimate was used.

Per IMWG criteria, CR: was defined as a negative immunofixation on serum and urine, and \<5% plasma cells in bone marrow; sCR: CR plus normal FLC ratio, and absence of clonal plasma cells by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein plus urine M-protein level \<100 mg/24 hours; PR: \>=50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by \>= 90% or to \<200 mg/24 hours; if serum and urine M-protein were not measurable, a decrease of \>=50% in difference between involved and uninvolved FLC levels was required instead of M-protein criteria. If serum and urine M-protein were not measurable and serum free light assay was also not measurable, \>=50% reduction in bone marrow plasma cells was required in place of M-protein, provided baseline bone marrow plasma cells percentage was \>=30%.

PFS: time from dates of randomization to initial documented PD per Sixty percent, bone marrow plasma cells (BMPC), Light chains, focal lesions per MRI, elevated Calcium, Renal failure, Anemia, Bone lesions (SLiM-CRAB) criteria, or date of death, whichever was first. SLiM-CRAB criteria: clonal BM PCs percentage (%): \>=60%, Involved: uninvolved serum free LC ratio \>=100, \>1 focal lesion on MRI studies, calcium:\>0.25 millimole/liter (mmol/L)(\>1 mg/dL) higher than upper limit of normal or \>2.75 mmol/L (\>11 mg/dL); creatinine clearance \<40 mL/min or serum creatinine \>177 micromole/liter (\>2 mg/dL); hemoglobin \<10 g/dL(\<6.5 mmol/L) or \>2 g/dL(\>1.25 mmol/L) lower than lower limit of normal;\>1 osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography-CT (PET-CT). Kaplan-Meier estimate was used.

Percentage of participants with symptomatic multiple myeloma with adverse prognostic features were reported. The International Staging System (ISS) for multiple myeloma (MM) was based on serum beta-2 microglobulin (S beta-2M) and serum albumin; that is, participants progressed to symptomatic multiple myeloma (SymT MM) with stage III (S beta2M\>= 5.5 mg/L) of ISS, Participants progressed to SymT MM with adverse cytogenetic characteristics (ACC), participants progressed to SymT MM with stage III of ISS or adverse cytogenetic characteristics. Adverse cytogenetic characteristics included Fluorescence in situ hybridization (FISH) findings of del(17p13), t(14;16), t(4;14), amp(1q21) or karyotype findings of t(4;14), del(17p) or a combination of these.

Response (IMWG Criteria) to first subsequent MM treatment: sCR: CR + normal FLC ratio and absence of clonal plasma cells by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry; CR: a negative immunofixation on serum and urine, and \<5% plasma cells in BM; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein plus urine M-protein \<100mg/24 hours; PR:\>=50% reduction of serum M-protein and \>=90% reduction in urine M-protein in 24 hour or to \<200 mg/24 hours; if serum and urine M-protein were not measurable, a decrease of \>=50% difference between involved and uninvolved FLC levels was required instead of M-protein criteria. If serum and urine M-protein and serum free light assay was also not measurable, \>=50% reduction in bone marrow plasma cells was required instead of M-protein, provided bone marrow plasma cells percentage was \>=30%.

Overall Survival (OS) was defined as the time from the date of randomization to the date of death. Median OS was estimated by using the Kaplan-Meier method.