Carfilzomib/Dexamethasone versus Bortezomib/Dexamethasone in Relapsed MM: Subgroup Analysis Based on Cytogenetic Risk Status of the ENDEAVOR Study

The randomized phase 3 ENDEAVOR study had previously demonstrated that carfilzomib plus dexamethasone (Kd) treatment resulted in significant improvement in progression-free survival (PFS) compared with bortezomib plus dexamethasone (Vd) in patients with relapsed multiple myeloma (MM); preplanned subgroup analysis based on baseline cytogenetic risk status in this study was reported.^1,2 In the ENDEAVOR trial, 929 eligible patients were randomized to receive carfilzomib (20 mg/m² on days 1 and 2 of cycle 1; 56 mg/m² thereafter) and dexamethasone (20 mg) or bortezomib 1.3 mg/m² (intravenous bolus or subcutaneous injection) and dexamethasone (20 mg) until disease progression, withdrawal of consent, or unacceptable toxicity. The high-risk group was defined as patients with t(4;14) or t(14;16) cytogenetics in ≥10% of screened plasma cells, or deletion 17p in ≥20% of screened plasma cells based on central review of bone marrow samples.

Overall, median PFS was lower in the high-risk cohort compared with the standard-risk cohort. However, patients treated with Kd achieved a PFS prolongation in both the high-risk (8.8 months vs 6.0 months; hazard ratio [HR], 0.646) and standard-risk (not reached vs 10.2 months; HR, 0.439) groups compared with Vd treatment. Kd treatment also resulted in higher overall response rates (ORRs; high risk: 72.2% vs 58.4%; standard risk, 79.2% vs 66.0%), a greater depth of response (≥complete response: high risk, 15.5% vs 4.4%; standard risk, 13.0% vs 7.9%), and longer duration of response (DOR; high risk, 10.2 months vs 8.3 months; standard risk, not reached vs 11.7 months) compared with Vd in both cytogenetic cohorts. Patients experienced higher rates of grade ≥3 adverse events with Kd therapy versus Vd in the high-risk (70.1% vs 63.1%) and standard-risk (73.9% vs 68.3%) groups. Incidence of grade ≥2 peripheral neuropathy was lower with Kd treatment in both the high-risk group (3.1% vs 35.1%; odds ratio, 0.059) and standard-risk group (6.4% vs 33.4%; odds ratio, 0.135). Taken together, the authors concluded that Kd treatment was superior to Vd in terms of PFS, ORR, and DOR regardless of baseline cytogenetic risk status, and showed a favorable overall benefit–risk profile in patients with high-risk relapsed MM.

1. Dimopoulos MA, et al. ASCO 2015. Abstract 8509.
2. Chng WJ, et al. ASH 2015. Abstract 30.