(038) Comparing clinical outcomes associated with two reduced intensity conditioning regimens for allogeneic stem cell transplant (busulfan/clofarabine and busulfan/fludarabine): A retrospective review

Poster Abstract:

Background:
Fludarabine is a purine analog commonly used in conditioning regimens for hematopoietic stem cell transplantation (HSCT).1 The use of fludarabine in reduced intensity conditioning (RIC) regimens stems from a phase 3 randomized trial that compared fludarabine-containing RIC regimens versus myeloablative conditioning (MAC) regimens in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS).2 Fludarabine-containing RIC regimens resulted in lower transplant-related mortality but had higher relapse rates when compared with the MAC regimens. 2 This trial showed that fludarabine-containing RIC regimens could be an effective option in patients that are not candidates for MAC regimens.2 Over the past few years, fludarabine has been placed on the Food & Drug Administration’s (FDA) drug shortage list.3 Due to the impact of the fludarabine shortage, the National Comprehensive Cancer Network (NCCN) guidelines provide alternative RIC regimens without fludarabine.1 These regimens include: pentostatin-based, clofarabine-based, cladribine-based, and cyclophosphamide-based regimens.1 Data supporting these regimens are limited to single arm studies with small patient populations.1 Clofarabine is a second-generation purine analog that has significant anti-leukemic activity and is FDA approved for the treatment of relapsed/refractory acute lymphoblastic leukemia and refractory AML.4 The CLORIC trial evaluated the use of a clofarabine-busulfan RIC regimen (CloB2A2) for HSCT.5 CloB2A2 was associated with a 63% overall survival, 57% leukemia-free survival, 40% relapse, and 3% non-relapse mortality all at 1 year. This trial concluded that CloB2A2 resulted in full engraftment in all patients and was well tolerated.5 This study expands on current literature and provides retrospective comparison of fludarabine and clofarabine containing RIC regimens.

Objectives:
The primary objective was the incidence of relapse-free survival at six months. Secondary objectives included overall incidence of graft-versus-host disease (GVHD) at day 100 and day 180 post-transplant, and transplant-related mortality, relapse, survival, and safety all at six months post-transplant.

Methods:
This single center, Institutional Review Board approved, retrospective chart review included adult patients who underwent RIC with either busulfan-clofarabine (Bu2Clo) or busulfan-fludarabine (Bu2Flu) HSCT at TriStar Centennial Medical Center from January 1st, 2022, through December 31st, 2022. Exclusion criteria consisted of patients < 18 years old or if patients received post-transplant cyclophosphamide (PTCy). A p-value of < 0.05 will be used to detect statistically significant differences in outcomes. Descriptive statistics were used for baseline characteristics. A non-inferiority test was used to test for equivalency between Bu2Clo and Bu2Flu in the primary outcome. Data was collected from the electronic medical record (EMR).

Results: Pending

Conclusions: Pending

References (must also be included in final poster): 1. Hematopoietic Stem Cell Transplant. National Comprehensive Cancer Network Guidelines. Version 1. 2023.
2. Scott, BL; et al. Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes. J Clin Oncol. 2017 Apr 10;35(11):1154-1161. doi: 10.1200/JCO.2016.70.7091. Epub 2017 Feb 13.
3. Fludarabine Injection. ASHP Drug Shortages. Ashp.org. 18 July 2023.
4. Fludarabine [package insert]. Bayer Healthcare Pharmaceuticals Inc; 2008.
5. Chevallier, P; et al. Results from a clofarabine-busulfan-containing, reduced-toxicity conditioning regimen prior to allogeneic stem cell transplantation: the phase 2 prospective CLORIC trial. Haematologica. 2014 Sep;99(9):1486-91. Epub 2014 Jun 20.