Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma

Abstract

Daratumumab plus pomalidomide and dexamethasone (pom-dex) was evaluated in patients with relapsed/refractory multiple myeloma with ≥2 prior lines of therapy who were refractory to their last treatment. Patients received daratumumab 16 mg/kg at the recommended dosing schedule, pomalidomide 4 mg daily for 21 days of each 28-day cycle, and dexamethasone 40 mg weekly. Safety was the primary end point. Overall response rate (ORR) and minimal residual disease (MRD) by next-generation sequencing were secondary end points. Patients (N = 103) received a median (range) of 4 (1-13) prior therapies; 76% received ≥3 prior therapies. The safety profile of daratumumab plus pom-dex was similar to that of pom-dex alone, with the exception of daratumumab-specific infusion-related reactions (50%) and a higher incidence of neutropenia, although without an increase in infection rate. Common grade ≥3 adverse events were neutropenia (78%), anemia (28%), and leukopenia (24%). ORR was 60% and was generally consistent across subgroups (58% in double-refractory patients). Among patients with a complete response or better, 29% were MRD negative at a threshold of 10^-5 Among the 62 responders, median duration of response was not estimable (NE; 95% confidence interval [CI], 13.6-NE). At a median follow-up of 13.1 months, the median progression-free survival was 8.8 (95% CI, 4.6-15.4) months and median overall survival was 17.5 (95% CI, 13.3-NE) months. The estimated 12-month survival rate was 66% (95% CI, 55.6-74.8). Aside from increased neutropenia, the safety profile of daratumumab plus pom-dex was consistent with that of the individual therapies. Deep, durable responses were observed in heavily treated patients. The study was registered at www.clinicaltrials.gov as #NCT01998971.

Figure 1.

Response rate in patients treated with daratumumab plus pom-dex. (A) Overall response rate. (B) Subgroup analysis of the overall best response. The dashed vertical line indicates 60.2%, which was the ORR in the total patient cohort. Exact 95% CIs are provided. ^aClassified as mild (total bilirubin 1.0-1.5× upper limit of normal or aspartate aminotransferase above upper limit of normal), moderate (total bilirubin >1.5-3.0× upper limit of normal), or severe (total bilirubin >3.0× upper limit of normal); 17% had mild impairment; 1% had moderate impairment; 0% had severe impairment. Patients with impaired hepatic function received fewer doses of daratumumab vs patients with normal hepatic function. ^bThe discrepancy with the demographics table is due to updated concomitant medication data. CrCl, creatinine clearance; DARA, daratumumab; sCR, stringent complete response.

Figure 2.

Response and duration of response. Responders from the response-evaluable population are represented. Black ovals indicate first response, white ovals indicate best response, and X indicates disease progression. sCR, stringent complete response.

Figure 3.

PFS and OS in patients treated with daratumumab plus pom-dex. At a median follow-up of 13.1 months, the median PFS (A) and median OS (B) are shown.