Real World Outcomes of Ruxolitinib Treatment of Steroid Refractory/Dependent Acute Graft Versus Host Disease

Aim:

Steroid-refractory and/or dependent acute graft versus host disease (SR/SD-aGVHD) is a life-threatening complication following allogeneic haematopoietic stem cell transplantation (HSCT). The REACH-2 study established ruxolitinib as standard of care compared to historical salvage options, however patients with lower gastrointestinal (GI) involvement still have poor outcomes¹. We aimed to review local outcomes of patients treated with ruxolitinib for SR/SD-aGVHD.

Method:

We performed a retrospective analysis of HSCT recipients treated between March 2021 and January 2024. The primary endpoint was overall survival (OS), with secondary endpoints including non-relapse mortality (NRM) and requirement for third line therapy.

Results:

We identified 37 patients with SR/SD-aGVHD, median age of 52 years at time of HSCT. All patients underwent T-replete HSCT using GCSF-stimulated PBSC. Donor source was matched sibling (27%), matched unrelated donor (49%), or haploidentical/mismatched (24%); with myeloablative conditioning in 35%. GVHD prophylaxis was cyclosporin/methotrexate (78%) or post-transplant cyclophosphamide/tacrolimus/mycophenolate (22%).

Acute GVHD occurred at median 41 days post-HSCT with grade III-IV disease in 48%, lower GI involvement in 68%, and skin-only disease in 27% at diagnosis. Following ruxolitinib commencement for SR/SD-aGVHD, the proportion of patients at D28/D56 with complete response was 62%/54% and overall response 78%/70%. Ruxolitinib failure occurred more frequently in patients with lower GI involvement compared to those without, with D28/D56 overall response of 69%/58% versus 100%/100%. Flares of aGVHD after initial response requiring third-line therapy occurred more frequent in patients with lower GI aGVHD (40% vs 0%).

At median follow-up of 159 days post ruxolitinib commencement, overall survival was 51% with mortality due to GVHD (56%), infection (22%) and relapse (6%). NRM occurred more frequently in patients with lower GI aGVHD (64% vs 8%).

Conclusion:

Our single-centre data supports ruxolitinib as second-line therapy for SR/SD-aGVHD. However, patients with lower GI involvement remain at significant risk for non-sustained response requiring third-line therapy and non-relapse mortality.

References:

1. Zeiser R, von Bubnoff N, Butler J, Mohty M, Niederwieser D, Or R, Szer J, Wagner EM, Zuckerman T, Mahuzier B, Xu J, Wilke C, Gandhi KK, Socié G; REACH2 Trial Group. Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease. N Engl J Med. 2020 May 7;382(19):1800-1810. doi: 10.1056/NEJMoa1917635. Epub 2020 Apr 22. PMID: 32320566.

Henden:Astra Zeneca: Honoraria; Astellas: Honoraria; Gilead: Honoraria.