Daratumumab Plus Pomalidomide-Dexamethasone: Deep MRD Responses in Heavily Treated Myeloma
This phase 1b study evaluated daratumumab combined with pomalidomide-dexamethasone in 103 heavily pretreated patients with relapsed/refractory multiple myeloma, achieving an overall response rate of 60% including 58% in double-refractory patients. Among complete responders, 29% achieved MRD negativity at 10^-5 by next-generation sequencing, with a median overall survival of 17.5 months. The safety profile was manageable, with neutropenia being the most common grade 3+ event, supporting this combination as a viable salvage regimen.
The original study
Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma.
- Authors
- Chari A, Suvannasankha A, Fay JW, Arnulf B, Kaufman JL, Ifthikharuddin JJ, et al.
- Journal
- Blood
- Type
- Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
- PMID
- 28637662
Original 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.