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
Authors: Varga Cindy , Robinson Myra , Davis James , Hashmi Hamza , Martin Thomas , Kumar Anupama Deepa , Sborov Douglas W , Wagner Charlotte B , Hansen Doris K. , Castaneda Omar , Shune Leyla O. , DeJarnette Shaun , Afrough Aimaz , Anderson Larry D , Dhakal Binod , Smith Kinaya , Herr Megan M , Richard Shambavi , Lieberman-Cribbin Alex , Sherbenou Daniel W. , Forsberg Peter A. , Voorhees Peter M. 
Published: December 2024

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 &gt;8g/dL, an absolute neutrophil count (ANC) &gt; 500/mm3 and a platelet count of &gt;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 &gt; 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 (&gt;50%), 2 patients had ANC &lt;1000/mm3 and 11 patients (25.6%) had thrombocytopenia (platelets &lt;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 &gt;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.