Efficacy of Stem Cell Boost (SCB) for Chimeric Antigen Receptor T Cell (CAR-T)-Related Hematologic Toxicity in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)- a Multi-Center Real World Experience

Background: Cytopenias are a known complication of CAR-T therapy in patients with RRMM. Although cytopenias can be expected immediately following T cell infusion, there is a subpopulation of patients who experience severe and persistent cytopenias. SCB with cryopreserved CD34+ stem cells may be an alternative to prolonged use of growth factor and transfusion support. Davis et al. (TCT 2023) recently reported on a series of 19 RRMM patients who received SCB following BCMA-directed CAR T therapy. Herein, we will describe the clinical characteristics, hematopoietic reconstitution and outcomes in a larger cohort with CAR-T-related hematological toxicity. Methods: This was a multicenter study consisting of data from the US Multiple Myeloma Immunotherapy Consortium comprising of 12 academic institutes. Patients were included if they received SCB following commercial CAR T between 6/2021 and 3/2024. Due to a paucity of historical itemized cell count data, a hemoglobin (Hgb) of >8g/dL, an absolute neutrophil count (ANC) > 500/mm³ and a platelet count of >50K/L were used to define cell count recovery. Progression-free survival (PFS) and overall survival (OS) were evaluated with Kaplan Meier methods.Selective data elements were only available at some sites. Results: 42 patients were included in this analysis. The median age was 65 (range: 39 to 79), 59.5% were male and 14.2% were African American. A third of patients had ISS stage III disease, 54.8% had extramedullary disease and 35.7% had high risk cytogenetics. The median number of prior lines of therapy was 6 (range, 4-15). 42.9% were penta- and 83.3% were triple-class refractory. Thirty-five patients (81.0%) received bridging therapy (BT), of which18 were administered cytotoxic chemotherapy (DCEP. PACE, or HyperCVAD). Only 7 patients attained a > partial response to BT while the remainder either progressed or achieved stable disease. Immediately prior to CAR T, 33% of patients had high bone marrow plasma cell burden (>50%), 2 patients had ANC <1000/mm³ and 11 patients (25.6%) had thrombocytopenia (platelets <50K). 26 patients received ide-cel with a median dose of 416.9 CAR + T cells (range; 275-496.4) and 16 patients received cilta-cel with a median dose of 0.6 CAR + T cells/kg (range; 0.41-0.75). Forty patients (95.2%) developed cytokine release syndrome (95% grade ½). All but one patient required GCSF support and 23 patients (53.5%) received a thrombopoietin agonist. Details related to the stem cell infusions were available in 35 of 42 patients. The median stem cell dose was 2.9 million CD34+ cells/kg (range: 1.76-23.55) given at a median of 53 days (range 24-871) after CAR T infusion. All patients achieved cell count recovery after a median of 22.5 days (range 9-93) following SCB. By day 90 post CAR T, the median ANC was 2110/mm³ (19-8790), the median Hb was 10.4g/dL (range 6.9-14.3), and the median platelet count was 134K/L (range 12-434). Twenty-one patients (50%) developed an infection (11 viral, 10 bacterial). 82.9% achieved a >VGPR,12.2% achieved a PR, one patient attained minimal response and one patient had disease progression. The median follow-up period was13 months (range 1-27). mPFS by CAR T product was 9.2 months for ide-cel and 11.0 months for cilta-cel. The 12-mo OS for ide-cel was 67.3% (95% CI: 48.7%-86%) and 76.2% (95% CI: 52.5%-99.8%) for cilta-cel. Thirteen patients died: 8 from myeloma, 2 from CAR-T-related complications, 2 from infection and 1 from an unrelated cause. Conclusions: Overall, SCB was safe and feasible in this heavily pretreated population. All patients successfully achieved count recovery with a rapid median time to recovery of less than 1 month. Accounting for the small sample size and enrichment for patients with high risk disease, there did not appear to be a clear impact on effectiveness, but additional data in a larger number of patients will be needed to better understand any beneficial or deleterious impact on efficacy.

Varga:Janssen: Honoraria, Research Funding; Arcellx: Research Funding. Martin:GSK: Honoraria; Roche: Honoraria; Pfizer: Honoraria; Sanofi: Research Funding; BMS: Research Funding; Janssen: Research Funding; AMGEN: Research Funding. Sborov:Pfizer: Consultancy, Research Funding; AstraZeneca: Consultancy; Bristol Myers Squibb: Consultancy; Abbvie: Consultancy; Society of Utah Medical Oncology: Membership on an entity's Board of Directors or advisory committees; Bioline: Consultancy; Genentech, Inc.: Consultancy; Arcellx: Consultancy; Janssen: Consultancy; Legend Biotech: Consultancy; GlaxoSmithKline: Consultancy; Sanofi: Consultancy; University of Utah, Huntsman Cancer Institute: Current Employment; Parexel, Keosys: Other: IRC; Binaytara Foundation: Honoraria. Wagner:Pfizer: Consultancy; Jazz: Research Funding. Hansen:Karyopharm: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Janssen: Consultancy; Pfizer: Consultancy. Castaneda:Janssen: Consultancy; BMS: Consultancy; Legend Biotech: Consultancy. Shune:BMS: Membership on an entity's Board of Directors or advisory committees; Norvatis: Membership on an entity's Board of Directors or advisory committees; Johnson and Johnson: Membership on an entity's Board of Directors or advisory committees. Afrough:Karyopharm Therapeutics: Honoraria, Other; Bristol-Myers Squibb: Honoraria, Other; K36 Therapeutics: Research Funding; Adaptive Biotech: Research Funding; Sanofi: Honoraria, Other; Abbvie: Research Funding. Anderson:Beigene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Prothena: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: DSMB; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Cellectar Biosciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Other: Travel Expenses, Research Funding. Dhakal:Medical College of Wisconsin: Current Employment; C4 therapeutics: Research Funding; Carsgen: Research Funding; Janssen: Honoraria, Research Funding, Speakers Bureau; Bristol Myers Squibb: Honoraria, Research Funding; Genentech: Consultancy, Honoraria; Karyopharm: Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Sanofi: Research Funding; Acrellx: Research Funding. Richard:Heidelberg Pharma: Research Funding; C4 Therapeutics: Research Funding; Gracell Therapeutics: Other: Steering Committee, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Steering Committee, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Sherbenou:Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jansen: Membership on an entity's Board of Directors or advisory committees. Forsberg:Johnson and Johnson, BMS: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Colorado Blood Cancer Institute: Current Employment; University of Colorado: Ended employment in the past 24 months; Karyopharm: Research Funding. Voorhees:AstraZeneca: Consultancy; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Lava Therapeutics: Consultancy; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.