Multiple myeloma (MM) patients with high cytogenetic risk have poor outcomes. In CASTOR,
daratumumab plus bortezomib/dexamethasone (D-Vd) prolonged progression-free survival
(PFS) versus bortezomib/dexamethasone (Vd) alone and exhibited tolerability in patients
with relapsed or refractory MM (RRMM).This subgroup analysis evaluated D-Vd versus
Vd in CASTOR based on cytogenetic risk, determined using fluorescence in situ hybridization
and/or karyotype testing performed locally. High-risk patients had t(4;14), t(14;16),
and/or del17p abnormalities. Minimal residual disease (MRD; 10-5 sensitivity threshold)
was assessed via the clonoSEQ® assay V2.0. Of the 498 patients randomized, 40 (16%)
in the D-Vd group and 35 (14%) in the Vd group were categorized as high risk.After
a median follow-up of 40.0 months, D-Vd prolonged median PFS versus Vd in patients
with standard (16.6 vs 6.6 months; HR, 0.26; 95% CI, 0.19-0.37; P < 0.0001) and high
(12.6 vs 6.2 months; HR, 0.41; 95% CI, 0.21-0.83; P = 0.0106) cytogenetic risk. D-Vd
achieved deep responses, including higher rates of MRD negativity and sustained MRD
negativity versus Vd, regardless of cytogenetic risk. The safety profile was consistent
with the overall population of CASTOR.These updated data reinforce the effectiveness
and tolerability of daratumumab-based regimens for RRMM, regardless of cytogenetic
risk status.ClinicalTrials.gov, NCT02136134 . Registered 12 May 2014.
