Teclistamab in relapsed/refractory light chain amyloidosis: A retrospective multicenter study by the German Society...

Systemic light chain (AL) amyloidosis is a rare, acquired protein misfolding disorder characterized by extracellular deposition of misfolded immunoglobulin light chain fibrils, resulting in organ damage. Treatment is based on anti-plasma cell regimens derived from multiple myeloma therapy. To date, no approved regimens exist for relapsed/refractory cases. This retrospective multicenter study, performed at 11 centers across Germany, evaluated the efficacy and tolerability of the treatment with teclistamab in 52 patients with relapsed/refractory AL amyloidosis. Hematologic response (≥very good partial response [VGPR]) was achieved in 81% of patients at Day 15, which increased to 95% at 3 months. Flow-minimal residual disease (MRD) was negative in 96% (23/24) of cases. Cardiac and renal responses (≥partial response [PR]) at 6 months were 65% and 78%, respectively. Cytokine release syndrome occurred in 37% of cases, with two classified as Grade 3 and none as Grade 4. Neutropenia Grade 3 or 4 occurred in 5/52 (10%) of patients. The 1-year overall survival was 83%, and the median overall survival was not reached after a median follow-up time of 8.8 months. Factors including difference between involved and non-involved free light chains (dFLC) ≥ 180 mg/L, N-terminal pro-brain natriuretic peptide (NTproBNP) ≥ 8500 pg/mL, glomerular filtration rate (GFR) < 20 mL/min/1.73 m², and dialysis did not significantly impact overall survival. In total, nine patients deceased, six of whom deceased due to bacterial infections. Patients receiving immunoglobulin replacement therapy had a 2.01 lower risk of infections Grade 3 or 4 and a 6.14 lower risk of death. Our findings demonstrate the efficacy of teclistamab in a heavily diseased and pretreated cohort with AL amyloidosis and highlight the necessity of a concomitant immunoglobulin replacement therapy.