Daratumumab, lenalidomide, and dexamethasone in relapsed/refractory myeloma: a cytogenetic subgroup analysis of POLLUX
Jonathan L Kaufman 1 , Meletios A Dimopoulos 2 , Darrell White 3 , Lotfi Benboubker 4 , Gordon Cook 5 , Merav Leiba 6 , James Morton 7 , P Joy Ho 8 , Kihyun Kim 9 , Naoki Takezako 10 , Philippe Moreau 11 , Heather J Sutherland 12 , Hila Magen 13 , Shinsuke Iida 14 , Jin Seok Kim 15 , H Miles Prince 16 , Tara Cochrane 17 , Albert Oriol 18 , Nizar J Bahlis 19 , Ajai Chari 20 , Lisa O'Rourke 21 , Sonali Trivedi 21 , Tineke Casneuf 22 , Maria Krevvata 21 , Jon Ukropec 23 , Rachel Kobos 24 , Hervé Avet-Loiseau 25 , Saad Z Usmani 26 , Jesus San-Miguel 27
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.
CITA DEL ARTÍCULO Blood Cancer J. 2020 Nov 3;10(11):111. doi: 10.1038/s41408-020-00375-2