Daratumumab, lenalidomide, and dexamethasone in relapsed/refractory myeloma: a cytogenetic subgroup analysis of POLLUX
Authors
Jonathan L Kaufman ; Meletios A Dimopoulos ; Darrell White ; Lotfi Benboubker ; Gordon Cook ; Merav Leiba ; James Morton ; P Joy Ho ; Kihyun Kim ; Naoki Takezako ; Philippe Moreau ; Heather J Sutherland ; Hila Magen ; Shinsuke Iida ; Jin Seok Kim ; H Miles Prince ; Tara Cochrane ; Albert Oriol ; Nizar J Bahlis ; Ajai Chari ; Lisa O'Rourke ; Sonali Trivedi ; Tineke Casneuf ; Maria Krevvata ; Jon Ukropec ; Rachel Kobos ; Hervé Avet-Loiseau ; Saad Z Usmani ; Jesus San-Miguel
High cytogenetic risk abnormalities confer poor outcomes in multiple myeloma patients. In POLLUX, daratumumab/lenalidomide/dexamethasone (D-Rd) demonstrated significant clinical benefit versus lenalidomide/dexamethasone (Rd) in relapsed/refractory multiple myeloma (RRMM) patients. We report an updated subgroup analysis of POLLUX based on cytogenetic risk. The cytogenetic risk was determined using fluorescence in situ hybridization/karyotyping; patients with high cytogenetic risk had t(4;14), t(14;16), or del17p abnormalities. Minimal residual disease (MRD; 10-5) was assessed via the clonoSEQ® assay V2.0. 569 patients were randomized (D-Rd, n = 286; Rd, n = 283); 35 (12%) patients per group had high cytogenetic risk. After a median follow-up of 44.3 months, D-Rd prolonged progression-free survival (PFS) versus Rd in standard cytogenetic risk (median: not estimable vs 18.6 months; hazard ratio [HR], 0.43; P < 0.0001) and high cytogenetic risk (median: 26.8 vs 8.3 months; HR, 0.34; P = 0.0035) patients. Responses with D-Rd were deep, including higher MRD negativity and sustained MRD-negativity rates versus Rd, regardless of cytogenetic risk. PFS on subsequent line of therapy was improved with D-Rd versus Rd in both cytogenetic risk subgroups. The safety profile of D-Rd by cytogenetic risk was consistent with the overall population. These findings demonstrate the improved efficacy of daratumumab plus standard of care versus standard of care in RRMM, regardless of cytogenetic risk.