Efficacy and safety of BCMA-targeted therapies in relapsed or refractory AL amyloidosis: a descriptive pooled analysis

Abstract B-cell maturation antigen (BCMA)–targeted therapies have emerged as promising treatment options for patients with relapsed/refractory immunoglobulin light-chain (AL) amyloidosis. However, comprehensive data on their efficacy and safety remain limited. We conducted a systematic descriptive pooled analysis of published studies reporting outcomes of BCMA-directed therapies including chimeric antigen receptor T-cell (CAR-T) therapies, bispecific antibodies (BsAbs), and antibody-drug conjugates (ADCs). The analysis included 256 patients. CAR-T therapy was administered to 89 patients (35%), BsAbs to 82 patients (32%), and ADCs to 85 patients (33%). The pooled overall response rate (ORR) was 83%, with CAR-T demonstrating 92% ORR; BsAbs, 89%; and ADCs, 68%. Deep hematologic responses (≥very good partial response) were achieved in ∼70% of CAR-T and BsAb recipients and 64% of ADC recipients. Minimal residual disease negativity was documented in 75% of evaluable CAR-T patients and in 86% of evaluable BsAb patients with reported data. Organ responses were observed in 30% of evaluable patients, with cardiac responses in 41%. Cytokine release syndrome (CRS) occurred in 74% of CAR-T and 49% of BsAb patients, predominantly grade 1 to 2. Grade ≥3 CRS was rare (9% in CAR-T and 1% in BsAb). Ocular toxicity was the predominant adverse event in ADC recipients (84% with any grade and 29% with grade ≥3). Grade ≥3 infections occurred in 13% of CAR-T, 20% of BsAb, and 6% of ADC patients. BCMA-targeted therapies result in high response rates with manageable safety profiles among patients with heavily pretreated AL amyloidosis, supporting continued investigation and clinical application of these approaches.