Crossover Patients With GVHD Respond to Ruxolitinib in REACH3 Trial

Patients with chronic graft-versus-host disease (GVHD) who crossed over to ruxolitinib (Jakafi) from the best available therapy (BAT) arm of the REACH3 study (NCT03112603) experienced response rates with ruxolitinib that were similar to those of patients who started the trial on ruxolitinib.¹

Results of the follow-up analysis were presented at the European Society for Blood and Marrow Transplantation (EBMT) 49th Annual Meeting and showed that at 24 weeks after crossover the overall response rate (ORR) of patients who transitioned to ruxolitinib (n = 69) was 47.8% (95% CI, 35.6%-60.2%), which was similar to the initial ORR of 49.7% (95% CI, 41.8%-57.6%) for patients who started on ruxolitinib (n = 165). According to Franco Locatelli, MD, who presented the data at the EBMT meeting, the ORR indicates that patients who cross over to ruxolitinib can still achieve a high response. However, only 3 patients who transitioned to ruxolitinib had a complete response (CR) compared with 11 patients in the initial ruxolitinib arm, and 43.5% (n = 30) of patients who crossed over had a partial response (PR) compared with 43% (n = 71) in the original treatment arm.

Among nonresponders who crossed over and were treated with ruxolitinib, 5 (7.2%) died during the course of treatment, 6 (8.7%) had a mixed response, and 4 (5.8%) experienced disease progression.

“[At] 24 weeks after enrollment, patients allocated to the BAT arm were allowed to cross over in the presence of either disease progression or poor mixed or unchanged response, toxicity to the selected BAT, or a chronic GVHD flare-up,” explained Locatelli, a professor of pediatrics at Sapienza University of Rome and head of the Department of Pediatric Hematology and Oncology at the IRCCS Bambino Gesù Children’s Hospital, also in Rome, Italy.

REACH3 also assessed best overall response (BOR) and found it to be significantly higher than the BOR of patients in the BAT arm: 76.4% vs 60.4% (P = .001), respectively. Patients on ruxolitinib had a 76.4% (95% CI, 69.1%-82.6%) BOR compared with the 79.7% BOR (95% CI, 68.3%-88.4%) observed in patients who crossed over to ruxolitinib. Patients who remained on BAT (n = 164) had a BOR of 60.4% (95% CI, 52.4%67.9%). Of these, 53.7% had a PR and 6.7% had a CR. In the ruxolitinib arm, 12.1% had a CR and 64.2% a PR; in the crossover arm, 5.8% had a CR and 73.9% had a PR.

Patients were randomized 1:1 to either 10 mg of ruxolitinib once daily or BAT plus steroids with or without a calcineurin inhibitor.

No new safety signals were observed in the crossover analysis. The main cause of death in the crossover group was infection seen in 50% of patients. Grade 3 or greater AEs were seen in 56.6% of the crossover group, 57% of the ruxolitinib group, and 57.6% of those still on BAT. Grade 3 serious AEs were similar across the 3 groups as well at 36.2%, 33.3%, and 36.7%, respectively.

AEs that led to treatment discontinuation were highest in the ruxolitinib-only group, at 16.4%, compared with 7.2% in patients who crossed over to ruxolitinib. After crossover, the most common all-grade and grade 3 or greater AEs were anemia (20.3%, 8.7%), upper respiratory tract infection (18.8% vs 4.3%), cough (15.9% vs 0%), and pyrexia (14.5% vs 1.4%).

“We can conclude that this analysis demonstrated that ruxolitinib has a manageable safety profile and leads to a high efficacy rate in patients with either steroid-refractory or steroid-dependent chronic GVHD who have experienced treatment with other systemic therapies,” said Locatelli.

REFERENCE

1. Russo D, Locatelli F, Teshima T, et al. Efficacy and safety of ruxolitinib in patients with steroid-refractory chronic graftversus-host disease after crossover in the phase 3 REACH3 study. Presented at: 49th Annual Meeting of the European Society for Blood and Marrow Transplantation; April 23-26, 2023; Paris, France. Abstract OS05-01.