Efficacy of Budesonide Monotherapy for Low Grade GI Gvhd after Post Transplant Cyclophosphamide

Introduction:

Post-transplant cyclophosphamide (PTCy) based GVHD prophylaxis reduces immunological complications after hematopoietic cell transplantation (HCT), thereby increasing the pool of suitable donors. While higher grade acute pattern GVHD is uncommon after PTCy, approximately 25-40% of patients will develop lower grade acute GVHD requiring therapy. We hypothesized that single-agent budesonide would provide effective monotherapy in patients who develop grade II isolated gastrointestinal (GI) GVHD. To evaluate this hypothesis, we conducted a retrospective cohort study including patients who received PTCy-based GVHD prophylaxis who were treated with budesonide monotherapy for grade II upper or lower GI acute GVHD.

Objective(s):

The primary objective of this study was to estimate 28-day and 56-day overall and complete response (CR) to budesonide monotherapy for isolated grade II acute GI GVHD in patients receiving PTCy for GVHD prophylaxis regimen following allogeneic HCT. Secondary objectives were incidence of progression to systemic therapy within 100 days of budesonide initiation, immunosuppression-free survival at 1 year, and overall survival.

Methods:

Included patients were >18 years old who received PTCy-based GVHD prophylaxis and allogeneic HCT. Patients who developed isolated grade II GI GVHD were initially treated with budesonide monotherapy within the first 100 days of transplant were included for analysis. Responses were defined per standard criteria with death and/or relapse considered as competing risks.

Results:

Between April 2015 to October 2021, 266 patients received PTCy-based GVHD prophylaxis after allogeneic HCT. Of those, 73 (27.4%) developed grade II isolated GI acute GVHD with the majority (n=63, 86.3%) treated with budesonide monotherapy. Patients were a median age of 67 (range 21-76) and 59% were male. The most common indications for transplant were myelodysplastic syndrome/myeloproliferative neoplasm (n=25, 40%) and acute myeloid leukemia (n=18, 29%) followed by non-Hodgkins lymphoma (n=9, 14%) and acute lymphoblastic leukemia (n=4, 6%). Most received a peripheral blood stem cell graft (60%) and donor types included, 56% haploidentical, 30% mismatched unrelated, and 11% matched unrelated. A total of 30 (48%) patients received myeloablative conditioning, 20 (32%) reduced intensity, and 12 (21%) non-myeloablative. The most common regimen received was fludarabine with melphalan and thiotepa (n=25, 40%), followed by fludarabine and melphalan (n=19, 30%), and fludarabine, cyclophosphamide and TBI (n=13, 21%). Stage 1 upper GI GVHD was seen in 98% of patients and stage 1 and 2 lower GI GVHD was seen in 29% and 6%, respectively. Overall response (OR) to budesonide at day 28 was 78.3%, with 53.3% of patients having a CR. OR at day 56 was 73.3%, with 61.7% having a CR. In patients with lower GI GVHD, OR at day 28 and 56 was 65% and 50%, respectively. In patients with solely upper GI GVHD, OR at day 28 and 56 was 85% for both. In patients who received budesonide monotherapy, 19 (30.2%) progressed to systemic steroids. The median time to initiation of systemic therapy was 35.5 days (range 1-289) from initiation of budesonide. Immunosuppression-free survival at 1 year was 17.7%. Overall survival at 1 year was 69%. Non-relapse mortality at 1 year was 16% (n=10) with 60% (n=6) of these cases attributable to GVHD.

Conclusion:

In patients who underwent allo-HCT with PTCy-based GVHD prophylaxis and developed isolated grade II GI GVHD, budesonide monotherapy resulted in excellent ORRs without the addition of systemic therapy, sparing patients toxicities associated with systemic treatment.

Perales:Incyte: Research Funding; Biotec: Research Funding; Novartis: Research Funding; Kite/Gilead: Research Funding; Nektar: Research Funding; Miltenyi: Research Funding; Allogene: Research Funding; OrcaBio: Current equity holder in private company; Omeros: Current Employment, Current equity holder in publicly-traded company; NexImmune: Current Employment, Current equity holder in publicly-traded company. Tamari:Orca Bio: Research Funding. Papadopoulos:Biogen: Current Employment, Current equity holder in publicly-traded company, Honoraria; Exelixis: Current Employment, Current equity holder in publicly-traded company, Honoraria; EpiKast: Current Employment; Regulus Therapeutics: Current Employment, Current equity holder in publicly-traded company, Honoraria; Leap Therapeutics: Current equity holder in publicly-traded company; AbbVie: Research Funding; Graviton Bioscience Corp: Current Employment; Apellis Pharmaceuticals: Current equity holder in publicly-traded company; Actio Biosciences Inc: Consultancy, Current equity holder in private company. Ponce:Evive: Consultancy; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; OncLive: Consultancy. Shaffer:Hansa Biopharma: Consultancy. Lin:Sanofi: Consultancy.

Budesonide for low grade upper/lower GI GVHD.