PGY2 Oncology Pharmacy Resident MD Anderson Cancer Center Houston, Texas, United States
Poster Abstract:
Background: Cyclophosphamide is used as a component of GVHD prophylaxis regimens for haploidentical, matched related donor (MRD), matched unrelated donor (MUD), and mismatched unrelated donor (MMUD) allogeneic hematopoietic cell transplant (alloHCT). Post-transplant cyclophosphamide (PTCy) preferentially targets allo-reactive T-cells while sparing non allo-reactive T-cells, leading to suppression to GVHD and graft rejection. PTCy is administered on days 3 and 4 following stem cell infusion in alloHCT and has been mostly shown to decrease the development of chronic GVHD, which is a major contributing factor for alloHCT-related morbidity and mortality.
Cyclophosphamide is a prodrug that is metabolized by various cytochrome P450 enzymes, including CYP2B6, 2C9, 2C19, 3A4, and 3A5, to its active metabolite. Additionally, CYP3A4 is responsible for the inactivation of cyclophosphamide. Azole antifungals are routinely used as antifungal prophylaxis in immunocompromised patients but azoles are known inhibitors of CYP enzymes, particularly CYP3A4.
The drug-drug interaction for the concomitant use of azole antifungals and cyclophosphamide is hypothesized to impact the safety and efficacy of PTCy and GVHD outcomes. However, this interaction has not been well studied. This study aims to evaluate the impact on GVHD and transplant-related outcomes when azoles are used concurrently with PTCy and provide valuable information pertaining to the potential clinical impact of antifungal drug-drug interaction with PTCy.
Objective: The primary objective of this study is to determine the incidence of acute and chronic GVHD for recipients of alloHCT receiving concomitant PTCy and antifungal therapy. The secondary objectives are to evaluate transplant related mortality, GVHD-free/relapse-free survival (GRFS), engraftment, incidence of relapse, and incidence of hemorrhagic cystitis attributed to PTCy.
Methods: This study is a retrospective cohort study consisting of patients aged 18 years and older who underwent their first alloHCT and received concomitant PTCy and antifungal therapy at The University of Texas MD Anderson Cancer Center between May 2021 and May 2022. Patients were included if they received alloHCT for a hematologic malignancy, administered PTCy 50 mg/kg on day 3 and 4 post-HCT, and given tacrolimus and mycophenolate mofetil for GVHD prophylaxis. Patients were excluded if they received a rituximab-based conditioning regimen, administered concomitant CYP inhibitors other than letermovir and/or azole antifungals between D0 and D+10 of alloSCT, or if the patient was on a research protocol. Patients were identified from the electronic database maintained by the Stem Cell Transplant and Cellular Therapy Department and from information query from electronic health records.
Results: pending
Discussion/conclusion: pending
References (must also be included in final poster): Broers AEC, de Jong CN, Bakunina K, et al. Posttransplant cyclophosphamide for prevention of graft-versus-host disease: results of the prospective randomized HOVON-96 trial. Blood Adv. 2022;6(11):3378-3385.
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Bolaños-Meade J, Hamadani M, Wu J, et al. Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis. N Engl J Med. 2023;388(25):2338-2348.
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