P-204: Carfilzomib, Dexamethasone, and Daratumumab (KdD) vs Kd: subgroup analysis of the CANDOR study by prior autologous stem cell transplantation, Lenalidomide exposure, or Lenalidomide refractory disease

Abstract

<h3>Background</h3> Widespread use of lenalidomide (Len) as standard first-line therapy for patients (pts) with multiple myeloma (MM) has resulted in a need for Len-sparing treatments in relapsed/refractory (RR) MM. The CANDOR study (NCT03158688) demonstrated prolonged median progression-free survival (PFS) with carfilzomib, dexamethasone, and daratumumab (KdD) versus Kd alone in pts with RRMM (28.6 vs 15.2 mo; Hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.45–0.78) that was consistent across clinically relevant subgroups (Dimopoulos Blood 2020). Autologous stem cell transplantation (ASCT) is frontline standard of care for MM, particularly for younger pts without severe comorbidities. Therapies that work consistently in pts with and without prior ASCT are needed, as many pts may defer or forego ASCT either due to ineligibility or alternatively selected therapy. This subgroup analysis of CANDOR reports overall efficacy and safety of KdD in RRMM pts with and without prior ASCT subdivided by Len-refractory and/or Len-exposed status. <h3>Methods</h3> Pts with RRMM (1–3 prior therapies) were randomized 2:1 to KdD or Kd (Dimopoulos Lancet Onc 2020). HR and corresponding 95% CI were estimated using a stratified Cox proportional hazard model. <h3>Results</h3> 62% (194/312) of pts in the KdD arm and 49% (75/154) of pts in the Kd arm received prior ASCT. With a median follow-up of 27 months, subgroup analyses of PFS were consistent with the primary analysis, suggesting PFS favorability of KdD vs Kd. In pts with prior ASCT, the PFS HR (95% CI) was 0.54 (0.37–0.77) overall, 0.35 (0.20–0.61) for Len-exposed, and 0.30 (0.15–0.59) for Len-refractory. In pts without prior ASCT, the PFS HR (95% CI) was 0.68 (0.44–1.05) overall, 0.62 (0.33–1.15) for Len-exposed, and 0.62 (0.31–1.22) for Len-refractory. Median PFS was estimable for some, but not all subgroups. In pts with prior ASCT, 2-year PFS rates for KdD and Kd were 55% vs 31% overall, 57% vs 15% for Len-exposed, and 57% vs 12% for Len-refractory. In pts without prior ASCT, 2-year PFS rates for KdD and Kd were 55% vs 44% overall, 53% vs 41% for Len-exposed, and 54% vs 39% for Len-refractory. Overall response rates, complete responses (CR), and minimal residual disease-negative CR rates favored KdD vs Kd consistently across all subgroups. Grade ≥3 adverse events (AE) were reported in 89.6% and 78.7% of pts receiving KdD and Kd in the ASCT subgroup and in 82.8% and 73.1% of pts without prior ASCT, with consistent rates across Len subgroups. Rates of treatment-emergent AEs leading to discontinuation of any study drug were 28.6% vs 21.3% for pts with prior ASCT and 25.9% vs 28.2% without ASCT for KdD vs Kd, respectively. <h3>Conclusion</h3> These findings further support the consistent clinical efficacy and safety of KdD among pts with RRMM with or without prior ASCT, including in the high unmet need group of pts with Len-refractory disease. The KdD regimen should be considered for all these pts beginning at first relapse.