Talquetamab induces deep responses in heavily pre-treated patients with systemic light-chain amyloidosis

Talquetamab, a CD3/GPRC5D T-cell engager approved for triple class exposed myeloma patients, inducing deep and durable responses. Very few cases of relapsed/refractory (R/R) light chain (AL) amyloidosis patients treated with talquetamab, were reported to date. We report six heavily pretreated R/R AL amyloidosis patients with severe end-organ damage (five with cardiac involvement), treated with talquetamab. Talquetamab induced rapid and deep responses: Five patients achieved complete response. (including MRD negativity in all three evaluable patients). At data cut-off, three patients were alive and relapse-free at 8, 15 and 24 months, and three patients died, after 1, 1.5 and 5 months since initiation of treatment. Five patients were not evaluable for organ response: (Three due to end-organ kidney disease, and two who died before organ response assessment). One patient achieved cardiac response. Two patients were referred to kidney transplantation after achieving CR. Cytokine release syndrome occurred in four patients, all grade 1–2, and immune effector cell associated neurotoxicity syndrome (ICANS) was reported in one patient (grade 2). Infections occurred in two patients (one grade 3, one grade 5). Congestive heart failure exacerbation occurred in two patients (grades 3 and 4). Our results support talquetamab as an effective therapy for RRAL patients, although larger-scale studies are needed to optimize earlier timing and patient selection.