Introduction: Chronic graft-versus-host disease (cGVHD) remains a major barrier to a successful hematopoietic stem cell transplantation (HSCT), associated with significant morbidity, increased risk of infection, and reduced quality of life. In cases refractory to first-line therapy with steroids, there is no standard of care for second line therapy. Ruxolitinib is a promising drug in this scenario and acts suppressing the proinflammatory signaling that mediates tissue damage and by the promotion of tolerogenic regulatory T (T-reg) cells.

Methods: We retrospectively analyzed the efficacy and safety of 35 patients receiving ruxolitinib for treatment of steroid-refractory cGVHD in two transplant centers, with the longest follow-up described to date.

Results: Median age was 54 years (range 23 - 73), and the most common diagnosis was acute leukemia (60%). There were 18 cases of related donor transplants and 17 cases of alternative donors (haploidentical in 9 and unrelated in 8). Most transplants were after reduced-intensity conditioning regimens (80%) and mobilized peripheral blood was used as the stem cell source in most cases (93%).

Patients treated with ruxolitinib had moderate (23/35; 66%) or severe (12/35; 36%) cGVHD before ruxolitinib was started and most patients (n = 23, 64%) had steroid-refractory cGvHD, compared to 13 (36%) patients with steroid-dependent cGvHD. The patients had a median of 3 organs affected (1-7) and the median number of previous lines of therapy was 2 (1-6). Response evaluation was based on 2014 National Institutes of Health criteria. Overall response rate was 89% and complete response rate was 29%, after a median of 4 weeks of therapy. Steroids were discontinued in 81% (n=25); and in 19% (n=6), a reduction > 50% on the dose of the steroids was possible. Median duration of treatment was 12 months (range 2-51). Median follow-up was 36 months (range 3-51). At follow-up, among the 27 patients still alive, 9 patients (37%) are still on treatment with ruxolitinib and remain in partial response (8 cases) or in complete response (1 case), and 18 patients (67%) stopped the drug, after achieving a sustained response (12 cases), due to lack of response (2 cases), due to toxicities (2 cases) or due to unavailability of the drug (2 cases). Therefore, 12 patients (44%) are free of any immunosuppression, and 10 (37%) are in use of ruxolitinib as the only immunosuppressive drug. Among 7 patients in which cGVHD relapsed after ruxolitinib withdrawal, 4 were re-exposed to the drug and all responded again.

There were only 2 cases of relapse of the underlying disease (1 patient with refractory acute myeloid leukemia and 1 case of Ph positive acute lymphoblastic leukemia) and both are again in sustained remission after salvage therapies. Median overall survival was not reached and overall survival at 3 years was 75%. Toxicities were mostly hematological, and resolved after dose reduction in most cases.

Conclusion: Our data, which represent the cohort of patients with cGVHD with the longest follow-up reported to date, support the use of ruxolitinib for refractory cGVHD. The high response rates with a favorable toxicity profile make ruxolitinib a promising therapeutic option. Randomized trials comparing ruxolitinib and other second-line therapies are currently underway and are waited to confirm evidence regarding the true efficacy and impact of ruxolitinib in steroid-refractory cGVHD.


No relevant conflicts of interest to declare.

OffLabel Disclosure:

ruxolitinib for treatment of steroid-refractory chronic GVHD - this drug has been used in the last couple years with impressive results

Author notes


Asterisk with author names denotes non-ASH members.