Abstract
BackgroundMultiple 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).MethodsThis 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.ResultsAfter 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.ConclusionThese updated data reinforce the effectiveness and tolerability of daratumumab-based regimens for RRMM, regardless of cytogenetic risk status.Trial registrationClinicalTrials.gov, NCT02136134. Registered 12 May 2014
Highlights
Multiple myeloma (MM) patients with high cytogenetic risk have poor outcomes
Intravenous daratumumab 16 mg/kg is approved as monotherapy in patients with heavily pre-treated relapsed or refractory multiple myeloma (RRMM) and in combination with bortezomib/dexamethasone (Vd) or lenalidomide/dexamethasone (Rd) in patients with multiple myeloma (MM) who received at least 1 prior line of therapy and in combination with pomalidomide/dexamethasone in patients with at least 2 prior therapies, including lenalidomide and a proteasome inhibitor [8]
Patients who received 1 prior line of therapy demonstrated the greatest benefit with daratumumab plus versus bortezomib/dexamethasone (Vd) (D-Vd), including a 78% reduction in the risk of disease progression or death versus Vd and a response of complete response (CR) or better (43% vs 15%; P < 0.0001) and minimal residual disease (MRD) negativity (10−5; 20% vs 3%; P = 0.000025)
Summary
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). In the primary analysis of the phase 3 CASTOR study of daratumumab plus Vd (D-Vd) versus Vd alone in patients with RRMM, at a median follow-up of 7.4 months, D-Vd significantly prolonged progression-free survival (PFS) and increased rates of minimal residual disease (MRD) negativity and demonstrated a tolerable safety profile [9, 10]. Patients who received 1 prior line of therapy demonstrated the greatest benefit with D-Vd, including a 78% reduction in the risk of disease progression or death versus Vd (median PFS, 27.0 months vs 7.9 months; HR, 0.22; 95% CI, 0.15–0.32; P < 0.0001) and a response of CR or better (43% vs 15%; P < 0.0001) and MRD negativity (10−5; 20% vs 3%; P = 0.000025). In CASTOR, no new safety concerns were observed with longer follow-up [11]
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