Journal: Blood cancer journal
This multicenter U.S. retrospective study evaluated 130 relapsed/refractory multiple myeloma patients treated with commercial elranatamab outside of clinical trials. The population was highly refractory (91% triple-class refractory, 49% penta-refractory), and nearly half (49%) had prior BCMA-directed therapy; only 22% would have met eligibility for the pivotal MagnetisMM-3 trial, underscoring a frailer, more heterogeneous real-world cohort.
Key efficacy findings:
- Overall response rate: 65%
- ≥Complete response: 36%
- Median PFS: 4.3 months
- Median OS: 14.6 months
These outcomes were inferior to those reported in MagnetisMM-3, consistent with higher-risk baseline features.
Prognostic factors and scoring:
- Elevated LDH and low hemoglobin independently predicted worse outcomes.
- These were combined into a new ALPS (Anemia–LDH Prognostic System) score, which effectively stratified patients for ORR, OS, PFS, and duration of response.
Impact of prior BCMA therapy:
- Prior BCMA exposure reduced depth of response to elranatamab.
- Patients treated with elranatamab within one year of prior BCMA therapy had poorer OS.
Toxicities and supportive care:
- Infections occurred in 38% of patients.
- Use of IVIG, modeled as a time-dependent covariate, was associated with improved infection-free survival and PFS, supporting proactive immune reconstitution strategies.
- Cytokine release syndrome rates were modestly lower than in MagnetisMM-3, but ICANS was more frequent in this real-world setting.
Overall, elranatamab showed substantial activity in a heavily pretreated, high-risk population, but with shorter durability of benefit and notable infectious and neurologic toxicity, emphasizing the importance of risk stratification (via ALPS), careful patient selection, and optimized supportive care (especially infection prophylaxis and IVIG use).