PN is a dose-limiting toxicity for some anti-MM agents, including the proteasome inhibitor (PI) bortezomib (V). Carfilzomib (K), a PI associated with low PN, was evaluated in 2 recent phase 3 studies in RRMM patients.
This analysis evaluated PN rates in ASPIRE (K [27 mg/m2]-lenalidomide [R]-dexamethasone[d] [KRd] vs Rd in relapsed MM) and ENDEAVOR (Kd [K 56 mg/m2] vs Vd in RRMM). We evaluated grade ≥2 PN during treatment, patient-reported outcomes (LS mean difference QLQ-C30 pain, FACT/GOG-neurotoxicity subscales), and progression-free survival (PFS) in patients with baseline history of PN.
In ASPIRE, grade ≥2 PN rate was low (8.9% [KRd] vs 8.0% [Rd]; OR [95% CI]: 1.132 [0.683, 1.876]; p=0.685). Pain subscale scores were similar between arms (ITT [95% CI]: -1.02 [-3.77, 1.73]; p=0.47). Median PFS was similar for K patients with BL grade ≥2 PN vs any baseline PN (24.2 vs 23.2 months). In ENDEAVOR, grade ≥2 PN rate during the study was significantly lower with Kd vs Vd (6.0% vs 32.0%; OR (95% CI) 0.137 (0.089, 0.210); p<0.0001). Patients had significantly lower pain (ITT [95% CI] -2.35 [-4.30, -0.39]; p=0.0186) and neurotoxicity subscale (Safety, [95% CI] 0.84 [0.40, 1.28]; p=0.0002) scores with Kd vs Vd. Median PFS (months) with Kd vs Vd in patients with BL history of grade ≥2 PN was 18.6 vs 5.6; HR [95% CI] 0.42 [0.266, 0.677], and 18.7 vs 9.4; HR [95% CI] 0.54 [0.410, 0.715] in patients with any baseline PN.
In ENDEAVOR, Kd resulted in less PN vs Vd; in ASPIRE, PN rate was similar for KRd vs Rd. Median PFS was longer with KRd and Kd vs Rd and Vd, respectively, in patients with BL grade ≥2 PN. Improved pain and neurotoxicity outcomes with K may be attributed to better disease control and/or lower PN rates.