Background
Phase 3, open-label, parallel-controlled, randomized trial at 41 hospitals in China. N=295 randomized (full analysis set 289). Adults with RRMM after ≥1 prior line, not lenalidomide-refractory; all Asian. Felzartamab is a CD38 antibody with preserved ADCC/ADCP but attenuated CDC activity.
Results
Interventions and follow up: Arm A: Felzartamab 16 mg/kg IV (D1 and D4 wk 1, weekly wk 2–12, q2wk wk 13–24, then q4wk) + lenalidomide 25 mg D1–21/28 + dexamethasone 40 mg weekly (20 mg if >75 y), n=195
Arm B: Lenalidomide + dexamethasone, n=100
Randomization: 2:1
Primary endpoint: PFS by independent review committee
mFollow up: 34.5 mo (IQR 16.8–40.2) vs 28.7 mo (IQR 10.8–38.8)
Results: PFS: 18.9 mo (95% CI 13.6–24.0) vs 10.4 mo (95% CI 5.8–13.9), HR 0.62 (95% CI 0.45–0.86), P=.0035
OS: NR
ORR: NR in abstract
Arm B: Lenalidomide + dexamethasone, n=100
Randomization: 2:1
Primary endpoint: PFS by independent review committee
mFollow up: 34.5 mo (IQR 16.8–40.2) vs 28.7 mo (IQR 10.8–38.8)
Results: PFS: 18.9 mo (95% CI 13.6–24.0) vs 10.4 mo (95% CI 5.8–13.9), HR 0.62 (95% CI 0.45–0.86), P=.0035
OS: NR
ORR: NR in abstract
Adverse events
Hematologic G3–4: neutropenia 55% vs 23%, lymphopenia 41% vs 15%, leukopenia 39% vs 11%, thrombocytopenia 26% vs 11%, anemia 17% vs 20%
Infection G3–4: pneumonia 23% vs 13%, URTI 8% vs 2%
Other G3–4: hypokalemia 16% vs 10%
Serious AE (most common): pneumonia 22% vs 10%
Treatment-related deaths: 6% (11/192) vs 2% (2/97)
Infection G3–4: pneumonia 23% vs 13%, URTI 8% vs 2%
Other G3–4: hypokalemia 16% vs 10%
Serious AE (most common): pneumonia 22% vs 10%
Treatment-related deaths: 6% (11/192) vs 2% (2/97)
Conclusions
Felzartamab + Rd significantly prolonged PFS vs Rd in Chinese patients with RRMM, supporting it as a potential new treatment option in this population.
Key Limitations
Open-label; Chinese/Asian population only, limiting generalizability. Comparator Rd is no longer the standard second-line backbone in many regions (daratumumab-, isatuximab- or carfilzomib-based triplets). OS not reported. Higher rates of cytopenias, pneumonia and treatment-related deaths (6% vs 2%) with the experimental arm. Control-arm PFS (10.4 mo) is short vs historical Rd/DRd trials.
Clinical Context
Adds a CD38 antibody with reduced CDC activity to the anti-CD38 + Rd class (daratumumab: POLLUX; isatuximab: IKEMA-type backbones). Regulatory status of felzartamab in multiple myeloma was not confirmed in this review. Guideline positioning (NCCN/ESMO) not established; does not alter standard anti-CD38 triplet recommendations outside China.