P-043: Stem Cell Boost for Persistent Cytopenias After BCMA-Directed Chimeric Antigen Receptor (CAR)-T Cell Therapy

Introduction: Hematological toxicity after CAR-T is common and often prolonged, resulting in transfusion and growth factor dependence. Emerging data has demonstrated that the infusion of autologous banked CD34+ stem cells can expedite hematological recovery.

Methods: We performed a retrospective review of all myeloma patients receiving autologous stem support after CAR-T across three institutions from 2020-2024. Dose and timing of administration of boost was determined by the treating physician. We included controls who were transfusion dependent at day ≥60 after CAR-T. This project was conducted as part of the IMF Immunotherapy Registry.

Results: Twenty-three patients received CD34+ stem cells between 2020-2024 after CAR-T therapy (8 ide-cel, 14 cilta-cel, 1 study drug). Median age at CAR-T was 65 years; 39% were women and 78% were White. Fourteen (61%) had at least one high-risk cytogenetic feature. Patients received a median of 6 prior lines of therapy (2-11); 43% received high-dose cyclophosphamide, 13% received bendamustine, and 30% received radiation within 3 months of CAR-T. At time of lymphodepletion, median blood counts were: absolute neutrophil count 2.0 x 10⁹/L (0.5- 3.2), hemoglobin 8.7 g/dL (6.2-12.2), platelet (Plt) 62 (8-201) x 10⁹/L. Median CD34+ boost dose was 3.29 x 10⁶/kg (1.08– 23.55 x 10⁶/kg), administered at a median of 62.5 days (14-263) after CAR-T, with variations across institutions (median of 49, 61.5, and 122 days, respectively). Median time post-boost to resolution of cytopenias was 8 days (1-161) for red blood cell (RBC) transfusion, 11 days (1-146) for Plt transfusion, 24 days (0-252) for Plt growth factors, and 13 days (2-86) for WBC growth factors (Table 1). Patients required a median of 4.5 RBC transfusions and 8 Plt transfusions pre-boost, compared to 0 RBC transfusions and 0.5 Plt transfusions post-boost. Those in the control arm required a median of 10 RBC transfusions and 9 Plt transfusions. At present, 57% of those who received stem cell support after cilta-cel and 88% who received stem cell support after ide-cel have relapsed, at a median of 295 days (179-1164) and 154 days (78-230), respectively.

	Median Days (Range), from Boost	Median Days (Range), from CAR-T
Resolution of RBC transfusions Boost Arm (N=11) Control Arm (N=13)	8 (1-161) n/a	57 (33-254) 61 (2-447)
Resolution of Plt transfusions Boost Arm (N=12) Control Arm (N=13)	11 (1-146) n/a	61.5 (25-199) 73 (27-449)
Resolution of Plt growth factor need Boost Arm (N=9) Control Arm (N=13)	24 (0-252) n/a	122 (54-370) 138 (61-311)
Resolution of WBC growth factor need Boost Arm (N=9) Control Arm (N=13)	13 (2-86) n/a	64 (34-258) 55 (24-1437)

Conclusions: We demonstrate that most patients had rapid resolution of transfusion and growth factor needs after receiving autologous CD34+ stem cells. This strategy may be particularly useful in patients with pre-existing cytopenias or recent exposure to cytotoxic chemotherapy or radiation.