A Single Center Experience of T Cell Redirecting Therapy Post Stem Cell Transplantation in Relapsed Multiple Myeloma

Introduction T-cell dysfunction hampers the efficacy of T cell redirecting therapy (TCRT), such as chimeric antigen receptor (CAR) T-cells or bispecific antibodies (bsAbs) and is often precipitated by multiple previous treatment lines. The infusions of hematopoietic stem cells (HSCs), in the setting of an auto-transplantation (ASCT) prior to TCRT could lead to immune reconstitution and improvement of the absolute lymphocyte count (ALC), a parameter associated with improved response to TCRT. Methods We analyzed 8 patients that underwent an ASCT within two years prior to TCRT (n=4 received CAR T-cells and n=4 bsAb therapy). Clinical parameters, including ALC before ASCT and TCRT, and clinical outcomes were captured. Results Median age of the patient cohort was 62 (31-71) years, 5/8 (62.5%) were male and median prior treatment lines were 6 (3-10). Median time from ASCT to TCRT was 193 (70-729) days. Of the 4 patients who received bsAb therapy (Teclistamab=3, Talquetamab=1), all had their ASCT as their last treatment prior to bsAbs, while the patients who received CAR T-cell therapy (4= Idecabtagene vicleucel) had at least one other treatment line between the ASCT and the CAR T-cell treatment. Furthermore, 3 of the 4 bsAB therapy patients had progressed on CAR T cell therapy prior to ASCT. ALC improved from values before ASCT to pre TCRT, 0.4 to 0.8 cells/ml for the whole cohort and 0.4 to 1 cells/ml for patients, where ASCT was the last treatment line before TCRT, p=0.03. Overall, 7/8 (88%) patients responded (5=CR, 2=VGPR). At a median follow up time of 4 months, mPFS was not reached. Conclusion While this cohort was limited by patient size and short follow-up, ASCT prior to TCRT appears safe and can improve ALC, which could improve efficacy of TCRT. Studies with larger patient sizes will be necessary to further test this therapeutic approach.