Cellular and T cell engager Immunotherapy

Category: Cellular and T cell engager Immunotherapy

Real-World Safety and Efficacy of BCMA Bispecific Antibodies in Relapsed and Refractory Light Chain Amyloidosis

(PA-071) Real-World Safety and Efficacy of BCMA Bispecific Antibodies in Relapsed and Refractory Light Chain Amyloidosis

Wednesday, September 17, 2025

Sandy Mazzoni, DO

Staff Hematologist
Cleveland Clinic

Introduction: Light Chain (AL) Amyloidosis is a protein processing disorder resulting in misfolded kappa or lambda light chains that deposit into healthy tissue leading to organ dysfunction. Amyloid production is shut down by achieving hematologic complete response (hCR) with anti-plasma cell therapy. With rapid hCR both overall survival (OS) and major organ deterioration progression free survival (MOD-PFS) improve. The current standard of care for newly diagnosed AL Amyloidosis is Daratumumab, Cyclophosphamide, Bortezomib and Dexamethasone with a hCR rate of 59.5% with median time to hCR of 67.5 days. There are two FDA approved B-cell maturation antigen (BCMA) bispecific antibodies (BiAbs) for the treatment of relapsed refractory multiple myeloma (RRMM) after 4+ lines of therapy, Teclistimab and Elranatamab. Both with an overall response rate (ORR) of ~61% in highly pre-treated MM. Studies are accessing safety and efficacy in newly diagnosed MM (NDMM) as combinations with other myeloma drug classes and as a maintenance regimen after ASCT. However, there is limited safety and efficacy regarding BCMA bispecific antibodies in AL Amyloidosis.

Methods:   Within our institution we identified 11 patients with RR AL Amyloidosis who received either Teclistimab or Elranatamab. We reviewed the charts for patient demographics, disease characteristics, treatment history and details regarding adverse events and response to BCMA BiAbs.

Results:   Of the 11 patients, median age 73 (60-80), 55% were female, 6 with cardiac involvement (1 with Mayo Stage IIIB, 4 with Mayo Stage IIIA), 7 with renal involvement, median plasma cell bone marrow involvement at diagnosis was 20% (4-94%), two cases with dual diagnosis with myeloma. One patient was not included in the safety and efficacy analysis due to disease related death during step-up dosing. Based on the ten patients included there was a 100% ORR, with 70% achieving a hCR, 30% VGPR. Median time to first response was 0.6 months (0.4-0.9). 4 of the 6 patients with cardiac amyloid had evidence of organ recovery with steady reduction in NT-pro-BNP. The data has not matured to determine DOR or any survival analyses; however, one patient has a DOR in hCR for >20 months. All patients received PJP prophylaxis. Two reports of grade 3 neutropenia with upper respiratory infection, both supported with IVIG and G-CSF. Three patients discontinued therapy after achieving hCR and maintain excellent disease control off treatment.

Conclusions:   In RR AL Amyloidosis we report an impressive ORR, hCR rate and time to hCR with a favorable safety profile. In AL Amyloidosis, there is an unmet need to improve both the hCR rate and time to hCR, especially those with advanced organ damage. Clinical trials to assess safety and efficacy for the use of BCMA BiAbs in AL Amyloidosis, specifically newly diagnosed, are essential in improving clinical outcomes. Studies will also need to address the best duration of therapy, a continued vs fixed course.