Efficacy and safety of BCMA-directed bispecific antibodies in relapsed and/or refractory systemic AL amyloidosis: A systematic review and meta-analysis.

BACKGROUND

Patients with relapsed/refractory (R/R) systemic light chain (AL) amyloidosis, particularly after daratumumab failure, face limited treatment options and challenging outcomes. B-cell maturation antigen (BCMA)-directed bispecific antibodies (BsAbs) have emerged as a potent strategy in multiple myeloma, yet their collective performance in AL amyloidosis remains to be systematically evaluated.

METHODS

Following PRISMA guidelines, we analyzed 8 independent cohorts (80 patients) treated with teclistamab or elranatamab. A random-effects model with Hartung-Knapp adjustment was employed to pool outcomes.

RESULTS

The pooled hematologic overall response rate (ORR) was 91% (95% CI: 87%-93%), with a deep hematologic complete response (hCR) rate of 64% (95% CI: 42%-82%). Rapid organ recovery was a hallmark of treatment: the pooled cardiac and renal response rates reached 59% (95% CI: 32%-82%) and 34% (95% CI: 14%-62%), cytokine release syndrome (CRS) was frequent but manageable (60%; 95% CI: 53%-67%), while immune effector cell-associated neurotoxicity syndrome (ICANS) remained rare (7%). However, Grade ≥ 3 infections were observed in 25% (95% CI: 15%-40%) of patients, potentially associated with T-cell dysfunction and therapy-induced hypogammaglobulinemia.

CONCLUSION

BCMA-directed BsAbs demonstrate potent hematologic efficacy in R/R AL, achieving deep and rapid light-chain clearance. This hematologic response translates into significant organ functional recovery. However, the high incidence of severe infections necessitates proactive antimicrobial prophylaxis, dose optimization, and immunoglobulin supplementation.