The Effectiveness of Teclistamab in Patients With Relapsed/Refractory Light Chain Amyloidosis: A Multicenter Retrospective Study

Aims/Background: Teclistamab is a B-cell maturation antigen (BCMA)-directed bispecific monoclonal antibody recommended for relapsed/refractory multiple myeloma (RRMM) management. However, some small-scale studies support the application of teclistamab in relapsed/refractory light chain (RRAL) amyloidosis, primarily secondary to multiple myeloma (MM). Therefore, this study evaluated the efficacy and safety profile of teclistamab in daratumumab-pretreated RRAL amyloidosis patients. Methods: After dose escalation, 19 patients across five centers, enrolled from October 2024 to July 2025, received teclistamab at a fixed dose (60 mg, n = 13) or weight-based administration (1.5 mg/kg, n = 6). Patients were followed up, and treatment response was monitored by evaluating hematologic, hepatic, cardiac, and renal involvement, as well as by examining the associated complications. The dosing frequency was reduced as hematologic efficacy improved, adjusted by the treating physician. Results: At a median 4.0-month follow-up (interquartile range [IQR], 3–8), teclistamab demonstrated profound hematologic responses and organ improvement. 94.7% of patients achieved a stringent difference between involved and uninvolved free light chain (dFLC) response at a median time of 18.5 days. The weight-based and fixed-dose groups had comparable time to stringent dFLC response (median 20.5 days [IQR, 18–26] vs 17.5 days [IQR, 11–27], p = 0.385). Furthermore, 68.4% of the patients showed a significant cardiac response. Adverse events observed following treatment included cytokine release syndrome (ten events, all ≤grade 2), immune effector cell-associated neurotoxicity syndrome (one event, grade 1), and associated infections (ten events, 4 ≥grade 3). Conclusion: These results indicate teclistamab as a practical option for daratumumab-exposed RRAL amyloidosis, supporting that fixed-dose strategy and timely reduction of dosing frequency guided by therapeutic efficacy appear to be feasible real-world approaches.