Oncology Pharmacy Resident Oregon Health Science University Portland, Oregon, United States
Poster Abstract:
Background: Retrospective registry data demonstrate that fludarabine was used in > 50% hematopoietic cell transplant and > 90% CAR-T procedures between 2010-2020. The sudden announced loss of availability prompted by the fludarabine drug shortage (June 2022) created a rapid need for alternatives particularly for use in CAR-T lymphodepletion. Bendamustine is immune suppressive with T-cell directed cytotoxicity, limited hematologic toxicity, and FDA-approved for use prior to tisagenlecleucel. However, limited evidence exists for expanded use in CAR-T applications across other products and hematologic malignancies. This study expands on existing literature for safety and efficacy on CAR-T outcomes using bendamustine as lymphodepletion.
Objective(s): The primary outcome was overall response rate. The secondary outcomes include progression-free survival, overall survival, depth of lymphodepletion, incidence and grade of CAR-T toxicities, infections, cytopenias, CD4 lymphopenia resolution, hospital length of stay, re-admission rate, and cytokine activity characterization.
Methods: This was a single-center, retrospective, chart review study including patients that received bendamustine prior to CAR-T (12/2021 – 06/2023). Descriptive statistics and Kaplan Meier estimates were utilized to summarize data.
Results: In total, 51 patients met inclusion criteria, including patients with diffuse large B-cell lymphoma (n=30), multiple myeloma (n=12), follicular lymphoma (n=5), mantle cell lymphoma (n=3), and primary mediastinal large B-cell lymphoma (n=1). 28 patients received > 4 lines of therapy before CAR-T. The overall response rate was 54.6%. The median progression-free survival was 99 days. The median overall survival was 292 days. Incidence of cytokine release syndrome (CRS) & immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade was 69% (n=35) and 29% (n=15), respectively. Ten patients (20%) developed infections within 90 days of CAR-T. New hospitalizations following CAR-T occurred at a frequency of 37% (n=19), with CRS being the most common reason for admission (58%). For hematologic toxicities, the incidence of neutropenia of any grade was 45% (n=23), 22% (n=11), and 8% (n=4) at 30, 60, and 90 days, respectively. The incidence of thrombocytopenia of any grade was 88% (n=45) at 30 days and 25% (n=13) for 60 days and 90 days.
Conclusions: These outcomes are consistent with previous literature reports evaluating bendamustine as lymphodepletion in terms of safety and efficacy. Additionally, these data encompass a larger patient demographic with more diverse disease states as well as multiple CAR-T products. Further subgroup analysis will be shown, including efficacy end points amongst the different disease states to elucidate which patient populations may benefit most from this alternative lymphodepleting regimen.
References (must also be included in final poster): References 1. Car T cells: Engineering immune cells to treat cancer. National Cancer Institute. Accessed October 29, 2023. https://www.cancer.gov/about-cancer/treatment/research/car-t-cells. 2.Mohty M, Minnema MC. Lymphodepleting Conditioning Regimens. In: Kröger N, Gribben J, Chabannon C, Yakoub-Agha I, Einsel eH, eds.The EBMT/EHA CAR-T Cell Handbook. Cham (CH): Springer; February 7, 2022.131-133. 3.Johnson PC, Abramson JS. Engineered T cells: CAR T cell therapy and beyond. CurrOncol Rep. 2022;24:23–31. 4.Turtle CJ, Hay KA, Hanafi LA, et al. Durable Molecular Remissions in Chronic Lymphocytic Leukemia Treated With CD19-Specific Chimeric Antigen Receptor-Modified T Cells After Failure of Ibrutinib. J Clin Oncol. 2017;35(26):3010-3020. doi:10.1200/JCO.2017.72.851 5.Maziarz RT, Diaz A, Miklos DB, Shah NN. Perspective: An International Fludarabine Shortage: Supply Chain Issues Impacting Transplantation and Immune Effector Cell Therapy Delivery. Transplant Cell Ther. 2022;28(11):723-726. doi:10.1016/j.jtct.2022.08.002 6.Schuster SJ, Tam CS, Borchmann P, et al. Long-term clinical outcomes of tisagenlecleucelin patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021;22(10):1403-1415. doi:10.1016/S1470-2045(21)00375-2 7.Ghilardi G, Chong EA, Svoboda J, et al. Bendamustineis safe and effective for lymphodepletion before tisagenlecleucelin patients with refractory or relapsed large B-cell lymphomas. Ann Oncol. 2022;33(9):916-928. doi:10.1016/j.annonc.2022.05.521
