TY - JOUR
T1 - Daratumumab, lenalidomide, and dexamethasone in relapsed/refractory myeloma
T2 - a cytogenetic subgroup analysis of POLLUX
AU - Kaufman, Jonathan L.
AU - Dimopoulos, Meletios A.
AU - White, Darrell
AU - Benboubker, Lotfi
AU - Cook, Gordon
AU - Leiba, Merav
AU - Morton, James
AU - Joy Ho, P.
AU - Kim, Kihyun
AU - Takezako, Naoki
AU - Moreau, Philippe
AU - Sutherland, Heather J.
AU - Magen, Hila
AU - Iida, Shinsuke
AU - Kim, Jin Seok
AU - Miles Prince, H.
AU - Cochrane, Tara
AU - Oriol, Albert
AU - Bahlis, Nizar J.
AU - Chari, Ajai
AU - O’Rourke, Lisa
AU - Trivedi, Sonali
AU - Casneuf, Tineke
AU - Krevvata, Maria
AU - Ukropec, Jon
AU - Kobos, Rachel
AU - Avet-Loiseau, Hervé
AU - Usmani, Saad Z.
AU - San-Miguel, Jesus
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/11/1
Y1 - 2020/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85094936712&partnerID=8YFLogxK
U2 - 10.1038/s41408-020-00375-2
DO - 10.1038/s41408-020-00375-2
M3 - Article
C2 - 33149130
AN - SCOPUS:85094936712
SN - 2044-5385
VL - 10
JO - Blood Cancer Journal
JF - Blood Cancer Journal
IS - 11
M1 - 111
ER -
