A Multicenter Phase II Trial of Ruxolitinib for Treatment of Corticosteroid Refractory Sclerotic Chronic Graft-Versus-Host Disease.

Purpose

Sclerotic chronic graft-versus-host disease (cGVHD) represents a highly morbid and refractory form of cGVHD, and novel therapies for sclerotic cGVHD are critically needed. This study aimed to determine the efficacy of ruxolitinib in patients with corticosteroid refractory sclerotic cGVHD.

Patients and methods

In a single-arm multicenter phase II trial (N = 47), adults with sclerotic cGVHD refractory to corticosteroids and ≥one additional line of systemic therapy for cGVHD received ruxolitinib for ≥six months (ClinicalTrials.gov identifier: NCT03616184). The primary end point was complete or partial response (PR) in skin and/or joint defined according to the 2014 National Institute of Health cGVHD Consensus Criteria.

Results

Following the use of ruxolitinib for a median of 11 months, PR in skin and/or joints was noted in 49% (95% CI, 34 to 64) at 6 months, with 45% having joint and fascia response and 19% having skin response. The duration of skin/joint response was 77% (95% CI, 48 to 91) at 12 months. Overall cGVHD PR was noted in 47% (95% CI, 32 to 61). Improvement in Lee Symptom Scale summary and skin subscale scores was noted in 38% of patients. With a cumulative incidence of treatment failure of 20.8% (95% CI, 10.0 to 34.1), nonrelapse mortality (NRM) of 2.2% (95% CI, 0.17 to 10.3), and no recurrent malignancy, failure-free survival (FFS) was 77.1% (95% CI, 61.3 to 87.0) at 12 months. Ruxolitinib was overall well tolerated with no new safety signals.

Conclusion

The use of ruxolitinib was associated with relatively high rates of skin/joint responses and overall cGVHD responses, improvement in patient-reported outcomes, low NRM, and high FFS in patients with refractory sclerotic cGVHD. Ruxolitinib offers an effective treatment option for refractory sclerotic cGVHD.

COI Statement

Disclosure of Conflicts of Interest. VRB reports participating in the Safety Monitoring Committee for Protagonist, serving as an Associate Editor for the journal, Current Problems in Cancer, and as a contributor for BMJ Best Practice, and receiving consulting fees from Imugene, research funding (institutional) from MEI Pharma, Actinium Pharmaceutical, Sanofi U.S. Services, Abbvie, Pfizer, Incyte, Jazz, and National Marrow Donor Program, and drug support (institutional) from Chimerix for a trial. HKC reports participating on ad hoc advisory boards for Incyte, clinical steering committee for Incyte, regional consulting for Sanofi, and research funding support by Opna. BKH reports participating on ad hoc advisory board for Incyte, Sanofi, and Rigel, Data Safety Monitoring Board for Angiocrine, and adjudication committee for CSL Behring. KG reports participating in advisory board for Novartis Pharmaceutics, Autolus and ImCheck Therapeutics. TN reports participating in advisory board for Medexus (uncompensated), and receiving clinical trial support (institutional) from Novartis and drug support for a clinical trial (institutional) from Karyopharm. SJL has received consulting fees from Mallinckrodt, Equillium, Kadmon, Novartis, Incyte; research funding from Amgen, AstraZeneca, Incyte, Kadmon, Pfizer, Sanofi and Syndax, and drug supply from Janssen. She is on clinical trial steering committees for Incyte and Sanofi. She is on the Board of Directors of the National Marrow Donor Program (uncompensated). There are no conflicts of interest for other authors.

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