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758 The Effect of Stem Cell Infusion on Immune Effector Cell Associated Hematotoxicity with BCMA CAR T in Multiple MyelomaClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 652. Multiple Myeloma: Clinical and Epidemiological: Immunological Effects of Sustained Responses in Multiple Myeloma
Hematology Disease Topics & Pathways:
Biological therapies, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Therapies, Adverse Events, Transplantation
Monday, December 11, 2023: 10:45 AM

Anannya Patwari, MD1*, Tanvi H. Patel, MD2*, Ramya Bachu, MD2*, Jean Esselmann, RN3*, Lisa Rein, ScM4*, Aniko Szabo, PhD1*, Abhishek Janardan, MD5*, Vineel Bhatlapenumarthi, MD5*, Evanka Annyapu, BS6*, Catherine E. Skoog, PA3*, Areyl Goff, MSN, RN, NP3*, Samer Al Hadidi, MD, MSc2, Sabarinath Venniyil Radhakrishnan, MD, MBBS6*, Sharmilan Thanendrarajan, MD2*, Maurizio Zangari, MD2, Frits van Rhee, MD, PhD2, Binod Dhakal, MD, MS7*, Anita D'Souza, MD, MS8, Meera Mohan, MD3 and Carolina Schinke, MD2

1Medical College of Wisconsin, Milwaukee, WI
2Myeloma Center, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR
3BMT and Cellular Therapy Program, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
4Department of Statistics, Medical College of Wisconsin, Milwaukee, WI
5Department of Hematology-Oncology, Medical College of Wisconsin, Milwaukee, WI
6Department of Medicine, Hematology-Oncology, Medical College of Wisconsin, Milwaukee, WI
7BMT and Cellular Therapy, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
8Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI

Introduction: In recent pivotal clinical trials and real-world studies of patients undergoing BCMA CAR-therapy for multiple myeloma (MM), a significant percentage have exhibited persistent Immune Effector Cell Associated Hematotoxicity (ICAHT). The resulting, sometimes profound and long lasting cytopenias, are associated with increased morbidity, such as high rates of infections and bleeding and complicate further anti-MM therapy once the patient relapses post CAR-T cell therapy. While growth factor support is widely applied in patients with ICAHT, the effects are usually short lived. Consequently, the use of CD34 selected stem cell boost in ICAHT as a more permanent solution has been described, however studies have been limited by small patient numbers and short follow up. Herein, we report on our multi-institutional experience at ICAHT in patients who received autologous BCMA CAR T therapy both in commercial and clinical trial settings.

Methods: We included recipients of autologous BCMA CAR T therapy at 2 large academic centers between 2020 and 2023. For this study, neutropenia was defined as an absolute neutrophil count (ANC) of ≤ 1000, thrombocytopenia as platelet counts ≤ 70,000 and anemia as hemoglobin ≤9 g/dL. ICAHT was characterized by the presence of any of these hematological abnormalities. The variables were assessed at 21 days, 3 months, and 6 months post CAR-T infusion. Median follow up time was 23 months.

Results : A total of 108 patients received BCMA CAR T therapy, 42 (39%) were treated on a clinical trial, 52 (48%) received commercial Idecabtagene vicleucel and 14/108 (13%) commercial Ciltacabtagene autoleucel. Baseline characteristics of the whole patient cohort are shown in table 1. The median age was 68 (range 57-69) years, with 63/107 (60%) being male. About 11% (n=12) patients were Black. 97/108 (90%) received at least one prior ASCT and the median prior lines of therapy was 5 (range 4-6). At D+21, ICAHT was observed in 68% (n=69/102) of patients, which reduced to 35% (n=30/86) and 27% (n=21/78) at the 3-month and 6-month assessments, respectively. Risk factors for ICAHT were the following: history of a prior ASCT, higher number of prior lines of therapy, a decreased platelet count prior to lymphodepletion and history of ICANS, which interestingly occurred in 11/69 (16%) patients who developed ICAHT but was not seen in those without ICAHT. About 97%(n=67/69) of patients with ICAHT had stem cells in storage and 26% (n=17/69) received a stem cell boost. The median time to stem cell boost following CAR T infusion was 116 (range 49-166) days. The median dose of stem cell infused was 3.91 (range 2.11-5.12) x106 CD34/kg cells. Unsurprisingly, patients with ICAHT who received a stem cell boost had significantly worse cytopenias prior to stem cell boost compared to those ICAHT patients without stem cell infusions at 120 days. Hgb was 8.4g/dL vs 10.2g/dL, p=0.02, and mean platelet levels were 30x109/L vs 54x109/L, p=0.01, compared to ICAHT patients without stem cell support. ANC levels were not significantly different between those two ICAHT groups (1700/mL vs 1500/mL), likely due to a higher use G-CSF support in ICAHT patients who received stem cell support (75% vs 55%, NS). Stem cell infusion significantly improved Hgb levels at 3 and 6 months follow up with an increase to 10.6g/dL, p=0.002, and 10.5g/dl, p=0.02, respectively. Similarly, platelet counts at 3- and 6-months post stem cell boost improved significantly to 131x109/L, p=<0.001, and 150x109/L, p=<0.001, respectively. ANC levels showed a nonsignificant increase to 2.8/mL and 3.9/mL at 3 and 6 months, yet, G-CSF support was no longer required. We further investigated whether the occurrence of secondary AML/MDS was associated with ICAHT, however these events were rare and developed in only 2 patients, one who had no ICAHT and the other one who had ICAHT without stem cell boost.

Conclusion: Nearly one-third of the patients who underwent BCMA CAR T therapy continued to experience ICAHT even at the 6-month post-infusion period. The utilization of a stem cell boost for managing ICAHT lead to significantly improved Hgb and platelet counts at 3 and 6 months follow up with also substantial improvement in ANC without further G-CSF requirements. These results suggest that the use of stem cell infusions in CAR-T cell induced ICAHT can improve cytopenia associated morbidities and facilitate further anti MM therapy post CAR-T relapse.

Disclosures: van Rhee: GlaxoSmithKline: Consultancy; Janssen Pharmaceuticals: Research Funding; EUSA Bio: Consultancy; Adicet Bio: Consultancy; Bristol Myers Squibb: Research Funding. Dhakal: Janssen, Karyopharm, GSK, Arcellx, GSK,Sanofi , Genentech, Pfi zer: Consultancy, Honoraria, Speakers Bureau. D'Souza: Janssen, Prothena: Consultancy; Imbrium, Pfizer, Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Abbvie, Sanofi, Takeda, TeneoBio, Caelum, Prothena: Research Funding. Mohan: Ionis Pharmaceuticals: Research Funding; Bristol-Myers Squibb Company: Research Funding; Celgene Corporation: Research Funding; GlaxoSmithKline plc: Research Funding; Takeda Pharmaceutical Company: Research Funding; Institutional KL2 Award: Other: Research Grant; Amgen Inc: Research Funding; Blood Cancer Today: Honoraria; MashupMD: Honoraria; MJH life sciences: Honoraria; Novartis: Research Funding; Bristol myers squibb/Celgene: Consultancy; Sanofi S.A: Consultancy, Research Funding; Pfizer: Consultancy. Schinke: Janssen: Consultancy, Honoraria; Pfizer: Honoraria; Arcellx: Consultancy.

*signifies non-member of ASH