Safety and efficacy of teclistamab in systemic immunoglobulin light chain amyloidosis
Rajshekhar Chakraborty, Divaya Bhutani, Mathew S. Maurer, Meera Mohan, Suzanne Lentzsch, Anita D’Souza
Abstract
Bispecific antibodies (bsAbs) targeting B-cell maturation antigen (BCMA) have transformed the landscape of relapsed/refractory (R/R) multiple myeloma, with single-agent response rates of 60–70% in patients who have undergone extensive prior treatments [ 1 , 2 , 3 ]. To date, two BCMA-targeting bsAbs have received accelerated approval by the Food and Drug Administration in R/R myeloma-teclistamab and elranatamab. Immunoglobulin light chain (AL) amyloidosis is a related clonal plasma cell disorder, in which, one of the pillars of treatment is effective clone-directed therapy to rapidly achieve a deep hematologic response, ideally a very good partial response (VGPR) or better [ 4 , 5 ]. Traditionally, clone-directed therapies in AL amyloidosis have been borrowed from successful anti-myeloma therapies, with the most recent example being the anti-CD38 monoclonal antibody daratumumab [ 6 ]. Presently, the standard-of-care regimen for newly diagnosed AL amyloidosis is daratumumab in combination with cyclophosphamide-bortezomib-dexamethasone (Dara-CyBorD), which leads to a hematologic complete response (heme-CR) and ≥VGPR rate of about 50 and 80% respectively [ 6 ]. However, a critical unmet need remains in the management of patients who have suboptimal hematologic responses to Dara-CyBorD or experience relapse following this regimen. BCMA-targeting bsAbs are an enticing treatment option for AL amyloidosis due to several reasons: (a) they lead to rapid achievement of deep hematologic responses in myeloma, which is critical for achieving organ response in AL amyloidosis; (b) lower incidence of severe cytokine release syndrome (CRS) compared to other T-cell redirecting immunotherapies such as chimeric antigen receptor T-cell therapy. However, there are no prospective or retrospective studies documenting the safety and efficacy of teclistamab in patients with AL amyloidosis, who were excluded from the clinical trials in R/R myeloma. Here, we present data on seven consecutive patients with AL amyloidosis with or without concurrent R/R myeloma from two academic medical centers, who were treated with teclistamab since its FDA approval on 10/25/2022. The data cut-off for follow-up was 10/1/2023. De-identified clinical data can be shared with other investigators upon request to the corresponding author (R.C.).