Efficacy and Safety of CD34+ Stem Cell Boost for Delayed Hematopoietic Recovery After BCMA Directed CAR T-cell Therapy.

INTRODUCTION: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment outcomes for patients with relapsed refractory multiple myeloma (RRMM). Despite supportive care with growth factors and thrombopoietin (TPO) mimetics, nearly half of the patients experience severe and prolonged cytopenias post CAR T infusion which have become a major therapeutic challenge for patients with RRMM. Given the successful use of CD34+ autologous hematopoietic stem cells for treatment of non- or delayed engraftment after allogeneic and autologous stem cell transplants, there is a need to explore the role of previously stored autologous stem cell as boosts for post CAR T cytpenias in RRMM.

METHODS: We performed a multicenter retrospective analysis of adult patients with RRMM who received previously collected and stored CD34+ stem cell boost post CAR T-cell therapy between 2 July 2020 and 18 January 2023. Indications for boost were determined per physician discretion and primarily included cytopenias and related complications.

RESULTS: Overall, a total of 19 patients received stem cell boost, at a median dose of 2.75 × 106 CD34+ cells/kg (range 1.76-7.38), given at a median of 53 days (range 24-126) after CAR T infusion. Eighteen (95%) patients successfully recovered hematopoiesis after stem cell boost with median time for neutrophil, platelet, and hemoglobin engraftment of 14 (range 9-39), 17 (range 12-39), and 23 (range 6-34) days post boost, respectively. Stem cell boost were well tolerated with no patients experiencing infusion reactions. While infections were common and severe prior to stem cell boost, only one patient experienced a new infection after boost. All patients had experienced independence from use of growth factors, TPO agonists, and transfusions at the last follow up.

CONCLUSIONS: Autologous stem cell boost can be effectively and safely used to promote hematopoietic recovery for post CAR T cytopenias in patients with RRMM. Stem cell boosts can be a veryeffective rescue measure for post CAR T cytopenias and related complications as well as supportive care needs.