Advancing Cutaneous GVHD Treatment

During the Tandem 2024 meetings Dr. Alina Markova from MSKCC presented the results of a study entitled Phase 2 trial of Ruxolitinib Cream for Chronic cutaneous GVHD which was selected as one of the Best Abstracts of the meeting. We delve deeper into the design and results of the study in this Q&A. 

What was the rationale behind your study? 
Limited topical treatment options exist for chronic cutaneous GVHD. Mainstays of topical therapy including topical steroids and topical calcineurin inhibitors may lead to incomplete response, prompting escalation of systemic therapy. Our aim was to investigate the efficacy and safety of a topical formulation of ruxolitinib for the treatment for chronic cutaneous GVHD.

What was the population studied? 
We enrolled allogeneic transplantation recipients age 12 years and older who had at least 2% of chronic cutaneous GVHD that was either nonsclerotic or superficially sclerotic.

Can you describe the intervention? 
In this double-blind, RCT, patients were randomized 1:1 in a split face/body design to application of the topical JAK 1/2 inhibitor ruxolitinib 1.5% cream to the right side of body; and placebo cream to the left side of body OR ruxolitinib to left, and placebo cream to the right. Patients applied these RIGHT and LEFT creams for 28 days, and then were permitted to crossover into an open label portion of the study where they could apply ruxolitinib cream to both side of the body

What was the primary outcome and how was the sample size estimated? 
The primary outcome was Day 28 comparison of reduction in % body surface area between ruxolitinib and placebo cream arms.  Using an average BSA of 1.8m2 (18,000 cm2 ) ; if we and treat, on average, 5.0% BSA per participant, we expect to have equivalent areas of 0.09m2 or 900cm2 of treatment and control areas per participant. So, based on these estimates, if we select lesional areas on a patient equivalent to 5% BSA (which is roughly 900cm2 for both treatment and control sides), and we have an estimated common standard deviation of 500, with 80% power, a two-sided test, an alpha level of 5%, and a correlation between treatment and control areas of 0.4, we can expect to detect a 327.1cm2 difference between treatment and control areas at the day 28 evaluation. The effect size calculation is based on a paired t-test. Since we do not have any pilot data for these calculations, the estimate for the standard deviation that utilized for these estimates comes from experience with conditions with a similar presentation

Can you briefly summarize the results? 
Ruxolitinib cream was safe and effective when compared to placebo cream for the treatment of chronic cutaneous GVHD. Responders to ruxolitinib cream had genomic signature differences in IL-12 signaling. Total body imaging may be a helpful tool in monitoring treatment response in cGvHD patients.

How will you move forward after the findings in this study?
We aim to further study its efficacy in acute and chronic GVHD in a multicenter prospective study.

Will there be further development of topical ruxolitinib in GHVD? 
We hope so, but it is up to Incyte.

Knowing what you know now, would you change anything in the design of the study?  
Would allow patients who were on shorter course of stable therapy (2 weeks) since we have the internal control of a split study design.

How do you envision the role of topical ruxolitinib in the future of GVHD treatment? 
I believe it will be used in combination with topical steroids and topical calcineurin inhibitors to minimize need for systemic therapies. It does not thin the skin (topical steroids) or have associated burning sensation (topical calcineurin inhibitors), so is a necessary alternative to reduce the current toxicities of available topical therapies.