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

Abstract

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 after 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 transplantations, there is a need to explore the role of previously stored autologous stem cells as a boost for post-CAR T cytopenias in RRMM. We performed a multicenter retrospective analysis of adult patients with RRMM who received previously collected and stored CD34+ stem cell boosts after 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. 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 after the boost, respectively. Stem cell boosts were well tolerated, with no patients experiencing infusion reactions. Although infections were common and severe before stem cell boost, only 1 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. Autologous stem cell boosts 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 very effective rescue measure for post-CAR T cytopenias and related complications, as well as supportive care needs.