Ruxolitinib Improves Outcomes in aGVHD Across Subgroups

Robert Zeiser, MD

Ruxolitinib (Jakafi) induced a strong, durable response across several subgroups of patients with steroid-refractory acute graft-versus-host disease (aGVHD), according to data from the REACH2 trial presented at the 25th Annual European Hematology Congress.¹

In a follow-up analysis to data first published in the New England Journal of Medicine in May 2020, investigators led by Robert Zeiser, MD, University Hospital Freiburg, Department of Hematology, Oncology and Stem Cell Transplantation, Freiburg, Germany, analyzed the effect of treatment on several subgroups of patients.

Zeiser and colleagues found that ruxolitinib improved response in adults aged 18 to 65 (OR, 3.12; 95% CI, 1.84-5.30) and those and those who did not did not respond to or who progressed on high doses of steroids (68.6% vs 32.6%; OR, 5.04; 95% CI 1.85-13.75).

Patients with aGvHD grade II had an ORR of 75.5% with ruxolitinib, the highest response in the study, compared with 50.9% for standard of care (OR 2.96; 95% CI, 1.30-6.76). The ORR for patients with skin involvement was 72.0% versus 47.3% in favor of the experimental arm (OR, 2.99; 95% CI, 1.55-5.79).

Ruxolitinib also induced high response rates in patients with varying degrees of disease severity, organ involvement, related or unrelated donor, and irrespective of prior GVHD therapy used.

The May data showed that overall response rate (ORR) at day 28 was 62.3% with ruxolitinib versus 39.4% with best available therapy (P <.001), in the total population. The durable ORR at 8 weeks, a secondary end point, was 39.6% versus 21.9%, respectively (P <.001). The median failure-free survival was 5 months versus 1 month, respectively (HR, 0.46; 95% CI, 0.35-0.60). The median overall survival was 11.1 months in the ruxolitinib group versus 6.5 months in the control group (HR, 0.83; 95% CI, 0.60-1.15).²

The multicenter, open-label, phase 3 REACH2 trial (NCT02913261) randomly assigned 309 patients with steroid-refractory aGVHD to ruxolitinib or investigator’s choice of best available therapy.

Investigators did not detect any new safety signals in this new analysis. In the previous findings, thrombocytopenia, anemia, and cytomegalovirus infection were the most common adverse events (AEs). Does modifications were required in 38% of the ruxolitinib arm and 9% of the control arm. AE-related treatment discontinuation occurred in 11% and 5% of the 2 arms, respectively.

The positive outcomes in REACH2 confirm the findings from the phase 2 REACH1 study, which were the basis of the May 2019 FDA approval of ruxolitinib for the treatment of adult and pediatric patients at least 12 years of age with steroid-refractory acute aGVHD. The study demonstrated that the combination of ruxolitinib with corticosteroids elicited a 57% ORR at day 28 in patients with steroid-refractory aGVHD, with a complete response rate of 31%.³

The open-label, single-cohort, multicenter phase 2 REACH1 study accrued patients aged at least12 years old who had received allogeneic hematopoietic stem cell transplantation and developed grade 2 to 4 steroid-refractory aGVHD. Patients had received up to 1 systemic treatment beyond corticosteroids for aGVHD. Of the 71 patients recruited on the trial, 49 patients were refractory to steroids alone, 12 patients had received ≥2 prior anti-GVHD therapies, and 10 patients did not otherwise meet the steroid-refractory definition by the FDA.

The ongoing phase 3 REACH3 trial (NCT03112603) is examining ruxolitinib versus best available therapy in patients with steroid-refractory chronic GVHD after bone marrow transplantation.

Ruxolitinib is also approved by the FDA as a treatment for patients with polycythemia vera who are intolerant of or have an inadequate response to hydroxyurea, as well as for the treatment of patients with intermediate or high-risk myelofibrosis.

References

1. Zeiser R. Ruxolitinib versus best available therapy in patients with steroid-refractory acute graft-versus-host disease: overall response rate by baseline characteristics in the randomized phase 3 REACH2 trial. Presented at: the 25th European Hematology Congress. June 11-21, 2020. Abstract #S255.
2. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease. New Engl J Med. 2020;382:1800-1810. doi:10.1056/NEJMoa1917635
3. FDA approves Jakafi (ruxolitinib) for the treatment of patients with acute graft-versus-host disease. Incyte. Published May 24, 2019. Accessed June 11, 2020. bit.ly/2WiRktX