A Randomized Phase II Crossover Study of Imatinib or Rituximab for Cutaneous Sclerosis after Hematopoietic Cell Transplantation

Sally Arai, Joseph Pidala, Iskra Pusic, Xiaoyu Chai, Samantha Jaglowski, Nandita Khera, Jeanne Palmer, George L. Chen, Madan H. Jagasia, Sebastian A. Mayer, William A. Wood, Michael Green, Teresa S. Hyun, Yoshihiro Inamoto, Barry E. Storer, David B. Miklos, Howard M. Shulman, Paul J. Martin, Stefanie Sarantopoulos, Stephanie J. LeeMary E.D. Flowers

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39 Scopus citations

Abstract

Purpose: Cutaneous sclerosis occurs in 20% of patients with chronic graft-versus-host disease (GVHD) and can compromise mobility and quality of life. Experimental design: Weconducted a prospective,multicenter, randomized, two-armphase II crossover trial of imatinib (200mg daily) or rituximab (375 mg/m2 i.v. weekly × 4 doses, repeatable after 3 months) for treatment of cutaneous sclerosis diagnosed within 18 months (NCT01309997). The primary endpoint was significant clinical response (SCR) at 6 months, defined as quantitative improvement in skin sclerosis or joint range of motion. Treatment success was defined as SCR at 6 months without crossover, recurrentmalignancy or death. Secondary endpoints included changes of B-cell profiles in blood (BAFF levels and cellular subsets), patient-reported outcomes, and histopathology between responders and nonresponders with each therapy. Results: SCR was observed in 9 of 35 [26%; 95% confidence interval (CI); 13%-43%] participants randomized to imatinib and 10 of 37 (27%; 95% CI, 14%-44%) randomized to rituximab. Six (17%; 95% CI, 7%-34%) patients in the imatinib arm and 5 (14%; 95% CI, 5%-29%) in the rituximab arm had treatment success. Higher percentages of activated B cells (CD27+) were seen at enrollment in rituximab-treated patients who had treatment success (P0.01), but not in imatinib-treated patients. Conclusions: These results support the need for more effective therapies for cutaneous sclerosis and suggest that activated B cells define a subgroup of patients with cutaneous sclerosis who are more likely to respond to rituximab.

Original languageEnglish
Pages (from-to)319-327
Number of pages9
JournalClinical Cancer Research
Volume22
Issue number2
DOIs
StatePublished - Jan 15 2016

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    Arai, S., Pidala, J., Pusic, I., Chai, X., Jaglowski, S., Khera, N., Palmer, J., Chen, G. L., Jagasia, M. H., Mayer, S. A., Wood, W. A., Green, M., Hyun, T. S., Inamoto, Y., Storer, B. E., Miklos, D. B., Shulman, H. M., Martin, P. J., Sarantopoulos, S., ... Flowers, M. E. D. (2016). A Randomized Phase II Crossover Study of Imatinib or Rituximab for Cutaneous Sclerosis after Hematopoietic Cell Transplantation. Clinical Cancer Research, 22(2), 319-327. https://doi.org/10.1158/1078-0432.CCR-15-1443