A randomized phase 2 trial of pomalidomide in subjects failing prior therapy for chronic graft-versus-host disease

Lauren M. Curtis, Alen Ostojic, David J. Venzon, Noa G. Holtzman, Filip Pirsl, Zoya J. Kuzmina, Kristin Baird, Jeremy J. Rose, Edward W. Cowen, Jacqueline W. Mays, Sandra A. Mitchell, Laura Parsons-Wandell, Galen O. Joe, Leora E. Comis, Ann Berger, Iskra Pusic, Cody J. Peer, William D. Figg, Liang Cao, Robert Peter GaleFrances T. Hakim, Steven Z. Pavletic*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

15 Scopus citations


Steroid-refractory chronic graft-versus-host disease (cGVHD) is a therapeutic challenge. Sclerotic skin manifestations are especially difficult to treat. We conducted a randomized phase 2 clinical trial (#NCT01688466) to determine the safety, efficacy, and preferred dose of pomalidomide in persons with moderate to severe cGVHD unresponsive to corticosteroids and/or subsequent lines of therapy. Thirty-four subjects were randomized to receive pomalidomide 0.5 mg per day orally (n = 17; low-dose cohort) or 2 mg per day at a starting dose of 0.5 mg per day increasing to 2 mg per day over 6 weeks (n = 17; high-dose cohort). The primary endpoint was overall response rate (ORR) at 6 months according to the 2005 National Institutes of Health cGVHD Response Criteria. Thirty-two patients had severe sclerotic skin and received a median of 5 (range, 2-10) previous systemic therapies. ORR was 47% (95% confidence interval, 30-65) in the intention-to-treat analyses. All were partial responses, with no difference in ORR between the cohorts. ORR was 67% (45%-84%) in the 24 evaluable subjects at 6 months. Nine had improvement in National Institutes of Health joint/fascia scores (P = .018). Median change from the baseline in body surface area involvement of skin cGVHD was −7.5% (–10% to 35%; P = .002). The most frequent adverse events were lymphopenia, infection, and fatigue. Eight subjects in the high-dose cohort had dose decreases because of adverse events. There was 1 death in the low-dose cohort from bacterial pneumonia. Our data indicate antifibrotic effects of pomalidomide and possible association with increases in concentrations of blood regulatory T-cell and interleukin-2. Pomalidomide 0.5 mg per day is a safe and effective therapy for advanced corticosteroid-refractory cGVHD. Key Points: • Pomalidomide is a safe and effective therapy for severe cGVHD, including sclerotic skin manifestations. • The recommended dose is pomalidomide 0.5 mg per day orally.

Original languageEnglish
Pages (from-to)896-907
Number of pages12
Issue number7
StatePublished - 18 Feb 2021
Externally publishedYes


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