Ruxolitinib REACH2 aGVHD Data Show Superiority Over Standard Care

Ruxolitinib (Jakafi) significantly improved the overall response rate (ORR) at day 28 versus best available therapy in patients with steroid-refractory acute graft-versus-host disease (aGVHD), according to findings from the phase 3 REACH2 trial published in the New England Journal of Medicine.^1,2

In the trial, the ORR at day 28 was 62% with ruxolitinib versus 39% with best available therapy (P <.001), meeting the primary end point of the trial. The durable ORR at 8 weeks, a secondary end point, was 40% versus 22%, respectively (P <.001). Further, the median failure-free survival was 5 months versus 1 month, respectively (HR, 0.46; 95% CI, 0.35-0.60).

No new safety signals emerged with ruxolitinib in REACH2, with a safety profile similar to previous studies of the JAK1/JAK2 inhibitor in patients with steroid-refractory aGVHD.

“Patients with acute graft-versus-host disease face life-threatening challenges with limited treatment options, particularly for the nearly half of individuals who do not respond to initial steroid therapy,” lead study investigator Robert Zeiser, MD University Hospital Freiburg, Department of Haematology, Oncology and Stem Cell Transplantation, Freiburg, Germany, said in a press release. "These new data from REACH2 showing superiority of [Jakafi] over current standard-of-care therapies add to a growing body of evidence on how targeting the JAK pathway can be an effective strategy in this difficult-to-treat condition.”

The multicenter, open-label, phase 3 REACH2 trial (NCT02913261) randomized patients with steroid-refractory aGVHD to ruxolitinib or investigator’s choice of best available therapy. 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 REACH 1 study, which were the basis of the May 2019 FDA approval of ruxolitinib for the treatment of adult and pediatric patients ≥12 years of age with&#8239;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 ≥12 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. &#8239;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. Novartis announces data showing Jakavi® (ruxolitinib) more effective than best available therapy in acute graft-versus-host disease. Posted April 23, 2020. https://bit.ly/3cJZkJ4. Accessed April 23, 2020.
2. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease [published online April 22, 2020]. New Engl J Med. 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 October 16, 2019.&#8239;https://bit.ly/2WiRktX