Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX

Abstract

In the POLLUX study, daratumumab plus lenalidomide/dexamethasone significantly reduced risk of progression/death versus lenalidomide/dexamethasone alone in relapsed/refractory multiple myeloma. We provide one additional year of follow up and include the effect on minimal residual disease and in clinically relevant subgroups. After 25.4 months of follow up, daratumumab plus lenalidomide/dexamethasone prolonged progression-free survival versus lenalidomide/dexamethasone alone (median not reached vs. 17.5 months; hazard ratio, 0.41; 95% confidence interval, 0.31-0.53; P<0.0001). The overall response rate was 92.9% versus 76.4%, and 51.2% versus 21.0% achieved a complete response or better, respectively (both P<0.0001). At the 10−5 sensitivity threshold, 26.2% versus 6.4% were minimal residual disease–negative, respectively (P<0.0001). Post hoc analyses of clinically relevant patient subgroups demonstrated that progression-free survival was significantly prolonged for daratumumab plus lenalidomide/dexamethasone versus lenalidomide/dexamethasone regardless of number of prior lines of therapy. Patients previously treated with lenalidomide or thalidomide and those refractory to bortezomib received similar benefits (all P<0.01). Treatment benefit with daratumumab plus lenalidomide/dexamethasone was maintained in high-risk patients (median progression-free survival 22.6 vs. 10.2 months; hazard ratio, 0.53; 95% confidence interval, 0.25-1.13; P=0.0921) and patients with treatment-free intervals of >12 and ≤12 months and >6 and ≤6 months. No new safety signals were observed. In relapsed/refractory multiple myeloma patients, daratumumab plus lenalidomide/dexamethasone continued to improve progression-free survival and deepen responses versus lenalidomide/dexamethasone. Trial Registration: clinicaltrials.gov identifier: 02076009.

Carfilzomib, lenalidomide and dexamethasone in patients with heavily pretreated multiple myeloma: A phase 1 study in Japan

“…(14) The elotuzumab regimen also showed a slightly lower ORR (79%) than the current study, providing further support for the use of the carfilzomib plus lenalidomide and dexamethasone regimen. Interim data from a phase 3 study by Dimopoulos et al (15) showed a comparable ORR for the daratumumab plus lenalidomide and dexamethasone regimen (93%) to that observed in the current study.…”

Bortezomib, cyclophosphamide, dexamethasone versus lenalidomide, cyclophosphamide, dexamethasone in multiple myeloma patients at first relapse

“…Likewise, the median PFS of 18·6 months with our RCD fixed‐dose nine‐cycle regimen was similar to that of 19·6 months obtained with continuous RD in patients at first relapse enrolled in the Pollux trial, that compared daratumumab plus lenalidomide plus dexamethasone versus lenalidomide plus dexamethasone (Dimopoulos et al , ). Likewise, in three other trials assessing continuous treatment with RD as control arm, the median PFS of this doublet ranged between 14·7 and 18·4 months (Lonial et al , ; Stewart et al , ; Moreau et al , ).…”

Daratumumab plus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma

“…22,23 Subgroup analyses from the phase 3 ENDEAVOR study demonstrated that carfilzomib (20/56 mg/m 2 dosing schedule) plus 20 mg dexamethasone demonstrated encouraging activity in lenalidomide-refractory RRMM patients. 7,8 The favorable tolerability of triplet or quadruplet daratumumabbased regimens observed across studies in MM 6,[19][20][21]24,25 provided the rationale for evaluating the combination of daratumumab and weekly carfilzomib in the multiarm phase 1b study MMY1001. Here, we report the safety, pharmacokinetics, and preliminary efficacy of daratumumab plus carfilzomib and dexamethasone (D-Kd) in patients with RRMM, including lenalidomide-refractory patients.…”