Detalle Publicación

Daratumumab, lenalidomide, and dexamethasone in relapsed/refractory myeloma: a cytogenetic subgroup analysis of POLLUX

Autores: Kaufman, J.L.; Dimopoulos, M. A.; White, D.; Benboubker, L.; Cook, G.; Leiba, M.; Morton, J.; Ho, P. J.; Kim, K.; Takezako, N.; Moreau, P.; Sutherland, H. J. ; Magen, H.; Iida, S.; Kim, J. S.; Prince, H. M. ; Cochrane, T. ; Oriol, A.; Bahlis, N. J.; Chari, A.; O'Rourke, L.; Trivedi, S.; Casneuf, T.; Krevvata, M.; Ukropec, J.; Kobos, R.; Avet-Loiseau, H.; Usmani, S. Z.; San Miguel Izquierdo, Jesús
Título de la revista: BLOOD CANCER JOURNAL
ISSN: 2044-5385
Volumen: 10
Número: 11
Fecha de publicación: 2020
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(R) 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.