Teclistamab Induces Rapid Responses in Patients with Relapsed/Refractory AL Amyloidosis

Introduction Systemic light chain (AL) amyloidosis is a rare disorder characterized by tissue deposition of amyloid fibrils derived from immunoglobulin free light chains. While daratumumab in combination with cyclophosphamide, bortezomib and dexamethasone (Dara-CyBorD) is the standard for upfront treatment of AL, management of relapsed/refractory (R/R) disease is often challenging, particularly in context of multiorgan dysfunction. Teclistamab was recently approved for treatment of R/R multiple myeloma (MM) and showed an overall response rate (ORR) of 63% (N Engl J Med 2022;387:495). Notable adverse effects (AEs) included cytokine release syndrome (CRS), neurologic, renal and hematologic toxicities, and infections. Efficacy of teclistamab in AL has not been previously reported. Here, we present a series of three patients who received treatment with teclistamab for R/R AL and MM. Methods In this retrospective study, we included all patients with R/R AL and MM who received teclistamab at two US academic centers between October 2022 and July 2023. We recorded all standard metrics, including serologic and biomarker data. Hematologic and organ responses were evaluated based on standard consensus criteria. Toxicity assessment was performed in accordance with the NCI CTCAE v5.0, except for CRS and neurotoxicity, which were graded according to the 2019 ASTCT criteria (BBMT 2019;25:625). Results We identified 3 patients; baseline characteristics are provided in Table 1 and treatment data in Table 2. Median age was 67 years (range, 54-70). All patients were male, and 2 had AL λ-type. At the time of teclistamab initiation, the median number of prior therapies was 7 (5-10), with all patients being refractory to a bortezomib, lenalidomide and daratumumab. Median iFLC was 228 mg/L (45.5-1272) with 10% median bone marrow (BM) plasmacytosis. In one patient with rapidly progressive multiple myeloma, BM FISH showed high-risk cytogenetic changes, including gain 1q, del 1p and del 17p. All patients were hospitalized for treatment initiation and received escalating doses of 0.06 mg/kg, 0.3 mg/kg and 1.5 mg/kg during the ramp-up phase. Subsequent treatment with target dose of 1.5 mg/kg was continued in the outpatient setting on a weekly basis. Monitoring for cytokine release syndrome (CRS) and neurologic toxicity was performed in accordance with institutional protocols. At a median follow-up of 49 days (44-58), 2 patients achieved hematologic responses (HR), with 1 complete hem