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.

Figure 1.

(A) PFS in the ITT population and (B) a forest plot summary of PFS HRs in subgroups by prior lines, prior therapies, treatment-free intervals. Kaplan- Meier analysis of PFS among patients in the ITT population. ^aTreatment-free interval was defined as the duration between the end date of the last line of prior therapy and randomization. ^bHigh-risk patients had any of t(4;14), t(14;16), or del17p as assessed by next generation sequencing. ^cStandard-risk patients had an absence of highrisk abnormalities. PFS: progression- free survival; ITT: intenttotreat; HR: hazard ratio; D-Rd: daratumumab/lenalidomide/dex amethasone; Rd: lenalidomide/dexamethasone; CI: confidence interval; NR: not reached; TFI: treatment-free interval; std: standard.

Figure 2.

PFS by cytogenetic risk status. Cytogenetic risk was assessed via nextgeneration sequencing. High-risk patients had any of t(4;14), t(14;16), or del17p. Standard-risk patients had an absence of high-risk abnormalities. PFS: progression- free survival; D-Rd: daratumumab/lenalidomide/dexamethasone; Rd: lenalidomide/dexamethasone; HR: hazard ratio; CI: confidence interval

Figure 3.

PFS by MRD at sensitivity threshold of (A) 10⁻⁵ and (B) 10⁻⁶. Kaplan-Meier estimates of PFS among patients in the intent-to-treat population. MRD-negative status was evaluated at sensitivity thresholds of 10⁻⁵ and 10⁻⁶ using bone marrow aspirate samples that were prepared using Ficoll and analyzed by the clonoSEQ^TM assay. PFS: progression-free survival; MRD: minimal residual disease; D-Rd: daratumumab/lenalidomide/dexamethasone; Rd: lenalidomide/dexamethasone.