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.

Conflict of interest statement

Conflict-of-interest disclosure: A.C. reports consultancy for, research funding from, and participation in advisory committees for Amgen, Array BioPharma, Celgene, Janssen, Millennium/Takeda, and Novartis. B.M.W. reports research funding and honoraria from Janssen. R.C. reports consultancy for and research funding from Janssen, Prothena, Takeda, and Karyopharm. J.L.K. reports consultancy for and research funding from Celgene, Novartis, and Incyte and consultancy for Pharmacyclics. S. Lentzsch reports consultancy for BMS, Janssen, and Celgene, participation in a speakers bureau for Takeda, and a leadership position and stock in Caelum Biosciences. S. Lonial reports consultancy and research funding from Millennium, Novartis, Bristol-Myers Squibb, Onyx, Celgene, and Janssen. J.W., K.N., C.C., N.Z.K., and T.A. are employees of Janssen Research & Development and own stock in Johnson & Johnson. The remaining authors declare no competing financial interests.

Figures

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.