PGY2 Oncology Pharmacy Residentt Nebraska Medicine Omaha, Nebraska, United States
Poster Abstract:
Background: The nucleoside analog, fludarabine, is an essential treatment component in conditioning regimens prior to allogeneic hematopoietic stem cell transplantation (HSCT) and for lymphodepletion before chimeric antigen receptor T-cell (CAR-T) therapy. Recent critical drug shortages of fludarabine beginning in 2022 prompted the need for increased utilization of alternative therapies such as cladribine and clofarabine for HSCT and bendamustine for CAR-T therapy. There is limited published literature describing the use of these alternative agents.
Objective: To evaluate the safety and efficacy of fludarabine alternatives when used before allogeneic HSCT and CAR-T therapy.
Methods: This retrospective study identified adults who had received cladribine or clofarabine for allogenic HSCT or bendamustine for CAR-T therapy between June 1, 2022, and June 30, 2023. Patients who received fludarabine alternatives will be matched 1:3 with those who received fludarabine-based treatment. Matching will be performed based on disease state, age, performance status, baseline organ function, and transplant conditioning regimen or CAR-T therapy. The primary outcome is the rate of adverse events experienced during initial hospitalization. Secondary outcomes include non-relapse mortality at Day 100 and 1-year post-treatment, graft vs host disease, cytokine release syndrome, immune effector cell-associated neurotoxicity, and hospital length of stay.
Results: Results of this research are pending.
Discussion/
Conclusion: This retrospective study seeks to identify safety concerns that may impact treatment decisions during the initial hospitalization of patients receiving fludarabine alternatives for conditioning and lymphodepletion. By providing further insight into the safety and efficacy of these regimens, this study hopes to help guide decision-making during times of drug shortage. Conclusion to follow finalized results.
References (must also be included in final poster): Alatrash G, Thall PF, Valdez BC, et al. Long-Term Outcomes after Treatment with Clofarabine ± Fludarabine with Once-Daily Intravenous Busulfan as Pretransplant Conditioning Therapy for Advanced Myeloid Leukemia and Myelodysplastic Syndrome. Biology of Blood and Marrow Transplantation. 2016;22(10):1792-1800. doi:10.1016/j.bbmt.2016.06.023
Andersson BS, Thall PF, Ma J, et al. A randomized phase III study of pretransplant conditioning for AML/MDS with fludarabine and once daily IV busulfan ± clofarabine in allogeneic stem cell transplantation. Bone Marrow Transplant. 2022;57(8):1295-1303. doi:10.1038/s41409-022-01705-7.
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Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. New England Journal of Medicine. 2019;380(1):45-56. doi:10.1056/nejmoa1804980
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