Ruxolitinib Significantly Improves ORR in Acute GVHD Compared With Best Available Therapy

June 30, 2020

Patients with steroid refractory acute graft-versus-host-disease (GVHD) have a better overall response rate (ORR) when treated with ruxolitinib compared with the best available therapy, according to results from a phase 3 trial presented at the European Hematology Association’s annual meeting.

Patients with steroid refractory (SR) acute graft-versus-host-disease (GVHD) have a better overall response rate (ORR) when treated with ruxolitinib compared with the best available therapy (BAT), according to results from a phase 3 trial presented at the European Hematology Association’s annual meeting.1

REACH2 was a phase 3 randomized trial that assessed the safety and efficacy of ruxolitinib compared with BAT. It included 309 patients who were randomized to receive either ruxolitinib (n = 154) or BAT (n = 155). Eligible patients were at least 12 years old, had undergone allogeneic hematopoietic stem cell transplant, had developed grade II to IV acute GVHD, and were also refractory to steroids.

Patients on BAT were permitted to cross over to the ruxolitinib arm if they had not responded by day 28. The primary end point was ORR at day 28. Patients randomized to the ruxolitinib arm started with 10 mg twice a day.

At data cut-off, 243 patients had discontinued (20.8% ruxolitinib vs 43.9% BAT). At day 28, the response rate was significantly higher among patients taking ruxolitinib (62.3%) compared with the BAT group (39.4%) (odds ratio [OR], 2.64; P <.001). The ORR favored patients treated with ruxolitinib for all grades of acute GVHD and baseline organ involvement. However, ORR was highest in patients with grade II acute GVHD (ruxolitinib 75.5% vs BAT 50.9%; OR, 2.96; 95% CI, 1.30-6.76) and for skin involvement (72.0% vs 47.3%; OR, 2.99; 95% CI, 1.55-5.79).

Across different subgroups of baseline characteristics, ruxolitinib “showed a consistent clinically meaningful treatment benefit,” the authors concluded.

A separate abstract used medical chart data to characterize chronic GVHD organ involvement, fibrotic manifestations, and treatment patterns.2 The authors evaluated patient charts for 93 patients with chronic GVHD. More than half (54%) previously had acute GVHD, and they were diagnosed with chronic GVHD a median of 87 days after hematopoietic cell transplant.

Seventy-one patients had organ involvement at diagnosis and 6% of patients had 3 or more organs involved at diagnosis. Most commonly patients had organ involvement in the skin, mouth, and eyes, and 87% of patients showed inflammatory processes and 59% of patients showed apparent fibrotic processes in at least 1 organ system.

Most patients received systemic steroids as their first line of treatment, which decreased in the second and third line. In the third line, 6% of patients used ruxolitinib and 16% used ibrutinib. The most common reasons for changing regimens in all lines of therapy were lack of efficacy, adverse event—related discontinuations, and progression of chronic GVHD. In later lines of therapy, patients were more likely to stay a little longer on therapy before changing.

“Currently, systemic steroids are the primary treatment, though many patients progress through multiple therapies due to a lack of efficacy and intolerable side effects,” the authors wrote, adding that the increased duration of therapy as patients progressed may be a result of few proven therapeutic options available. “Additional therapies are needed to address the underlying unmet need for patients with multiorgan involvement and fibrosis.”

References

1. Zeiser R, von Bubnoff N, Niederwieser D, et al. Ruxolitinib versus best available therapy in patients with steroid-refractory acute fraft-versus-host disease overall response rate by baseline characteristics in the randomized phase 3 REACH2 trial. Presented at: EHA25 2020; June 11-21, 2020; Abstract S255.

2. Salhotra A, Eiznhamer D, Hennegan K, Dehipawala S, Aggarwal SK. Presentation and management of chronic graft-versus-host disease in real-world clinical practice: a medical chart audit. Presented at: EHA25 2020; June 11-21, 2020; Abstract EP1436.