Efficacy of Ruxolitinib with Corticosteroids in Idiopathic Pneumonia Syndrome Post-Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Experience and Systematic Review

Background: Idiopathic Pneumonia Syndrome (IPS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a life-threatening complication with high morbidity and mortality. This study evaluates the effectiveness of Ruxolitinib, a JAK1/2 inhibitor that modulates the immune response, in combination with corticosteroids (CS), which have anti-inflammatory and immunosuppressive effects, in managing IPS after allo-HSCT.

Methods: The study includes a retrospective case series of three patients treated for IPS with Ruxolitinib and CS from the University of Kansas Medical Center and a systematic review of seven studies involving 346 cases, including our case series. Statistical analyses were conducted using SPSS.

Results: The case series included three patients with IPS after allo-HSCT who received ruxolitinib and CS. Patient A was a 72-year-old man with a history of acute myeloid leukemia (AML) in first complete remission (CR1), underwent allo-HSCT with a haploidentical donor with Fludarabine, Cyclophosphamide, and Total Body Irradiation (Flu/Cy/TBI) reduced intensity conditioning (RIC) and Post-Transplant Cyclophosphamide (PTCy), Tacrolimus (Tac) and Mycophenolate Mofetil (MMF) for GVHD prophylaxis, who developed five months after the transplant. Patient B was a 30-year-old man with a history of chemotherapy-refractory B-cell acute lymphoblastic leukemia (ALL) with CR1 after Brexucabtagene autoleucel chimeric antigen receptor (CAR) T-cell therapy who underwent allo-HSCT with HLA-match unrelated donor (MUD) with Busulfan and Fludarabine reduced-intensity conditioning given liver dysfunction and PTCy/Tac/MMF for GVHD prophylaxis, who developed IPS six months post-transplant. Patient C was a 22-year-old male with a history of AML in CR1, who underwent allo-HSCT with HLA-matched related donor with Cyclophosphamide and Busulfan myeloablative conditioning and Tacrolimus with Methotrexate (MTX) for GVHD prophylaxis, who developed IPS at ten months post-transplant. All three patients showed substantial improvement with no IPS-associated mortality. Of the 346 cases included in the systematic review, the median age was 46.6 years (range 5-72), and 62% were males. The primary disorders were acute leukemia (52%), chronic myeloid leukemia (12%), myelodysplastic syndrome (11%), Lymphoma (10%), and others (21%). Stem cell sources were peripheral blood (45%), bone marrow (49%), and cord blood (6%). Donor types involved match unrelated (55%), match related (36%), and mismatched related (4.5%). Most patients received myeloablative conditioning (81%). Acute GVHD was observed in 47% of cases, and chronic GVHD was observed in 38%. The primary treatment was CS (96%), with limited use of ruxolitinib (1%) and etanercept (9.5%). The mortality rate was 63.3%.

Conclusion: The combination of Ruxolitinib and CS for treating IPS post-allo-HSCT has shown promising results in the case series, with favorable response and improved survival. This underscores the urgent need for innovative treatment approaches. The systematic review further supports this call for new strategies in IPS management.

Ahmed:Kite, a Gilead Company: Research Funding; Bristol Myers Squibb: Consultancy. Abhyankar:CSL Behring, Miltenyi Biotec.: Research Funding; Incyte: Consultancy. McGuirk:CRISPR therapeutics: Consultancy; Caribou bio: Consultancy; Envision: Consultancy; BMS: Consultancy; Kite: Consultancy; Autolus: Consultancy; NEKTAR therapeutics: Consultancy; Sana technologies: Consultancy; Legend biotech: Consultancy; Allo Vir: Consultancy; Novartis: Consultancy. Mushtaq:Iovance Biotherapeutics: Research Funding.