TOPLINE

Among patients undergoing haploidentical hematopoietic stem-cell transplantation (HSCT), low-dose ruxolitinib, used in place of mycophenolate mofetil within a backbone of prophylactic antithymocyte globulin, calcineurin inhibitor, and short-course methotrexate, was associated with a lower incidence of grade II-IV acute graft-vs-host disease (GVHD). The regimen also reduced non-relapse mortality and improved GVHD-free relapse-free survival without a significant increase in infectious complications.

METHODOLOGY

• Acute graft-vs-host disease remains a major concern and is associated with serious complications and death in patients undergoing haploidentical stem-cell transplantation. Although ruxolitinib, a Janus kinase 1/2 (JAK1/2) inhibitor, has shown benefit in steroid-refractory GVHD and early prophylaxis studies, data from randomized trials in haploidentical HSCT remain scarce.
• To address this, researchers conducted a multicenter phase 3 trial of 206 patients (median age, 40 years; 52% men) with hematological malignancies undergoing their first myeloablative haploidentical HSCT.
• Patients were randomly assigned to receive either antithymocyte globulin, calcineurin inhibitor, short-course methotrexate, and low-dose ruxolitinib (n = 103), or standard prophylaxis with antithymocyte globulin, calcineurin inhibitor, short-course methotrexate, and mycophenolate mofetil (n = 103).
• Oral ruxolitinib was initiated on day 1 at 5 mg twice daily for patients weighing ≥ 50 kg or 5 mg once daily for those weighing < 50 kg, continued up to day 60, and then tapered to day 90 in the absence of grade II-IV acute GVHD.
• The primary endpoint was cumulative incidence of grade II-IV acute GVHD by day 100. Secondary endpoints included grade III-IV acute GVHD, chronic GVHD, non-relapse mortality, relapse, overall survival (OS), and GVHD-free relapse-free survival. The median follow-up duration among surviving patients was 26.4 months.

TAKEAWAY

• By day 100, the cumulative incidence of grade II-IV acute GVHD was 6.8% in the ruxolitinib prophylaxis group and 36.9% in the standard prophylaxis group (subdistribution hazard ratio [sHR], 0.15; P < .0001).
• The cumulative incidence of grade III-IV acute GVHD remained consistently lower in the ruxolitinib prophylaxis group than in the standard prophylaxis group at day 100 (1.9% vs 19.4%; sHR, 0.09; P < .0001), and at day 180 (4.9% vs 20.4%; sHR, 0.21; P = .0006).
• The cumulative incidence of non-relapse mortality was significantly lower with ruxolitinib prophylaxis (0 patients vs 6 patients; sHR, 0.16; P = .014), as was the incidence of moderate-to-severe chronic GVHD (5.0% vs 19.1%; sHR, 0.24; P = .0024). The risk of a GVHD-free relapse-free survival event was lower with ruxolitinib (hazard ratio [HR], 0.37; P < .0001), while relapse incidence did not differ significantly between groups.
• Adverse events occurred in 97% of patients in the ruxolitinib group and 98% in the standard group, and grade 3 or worse AEs occurred in 45% and 40%, respectively; 11 deaths occurred with ruxolitinib and 14 with standard prophylaxis, mainly from relapse. No treatment-related deaths were reported.

IN PRACTICE

“These findings support early JAK1/2 inhibition as a clinically relevant strategy for GVHD prevention in antithymocyte globulin-based haploidentical HSCT,” the study authors wrote, suggesting that “further studies are needed to confirm these findings in other transplantation platforms and populations.”

SOURCE

The study, led by Hengwei Wu, MD, and Zhuoyue Shi, MD, Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine in Hangzhou, China, and Wenming Shi, PhD, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China, was published online in The Lancet Haematology.

LIMITATIONS

The trial was conducted within an antithymocyte globulin-based haploidentical HSCT platform, limiting applicability to post-transplantation cyclophosphamide-based haploidentical HSCT, matched donor transplantation, and cord blood transplantation. The open-label design could have introduced performance and assessment bias despite blinded central adjudication. The cohort was drawn from Chinese centers, warranting validation in other populations and practice settings.

DISCLOSURES

This study was funded by the National Natural Science Foundation of China. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.