A Randomized Phase II Crossover Study of Imatinib or Rituximab for Cutaneous Sclerosis after Hematopoietic Cell Transplantation.
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:
We conducted a prospective, multicenter, randomized, two-arm phase II crossover trial
of imatinib (200 mg daily) or rituximab (375 mg/m(2) 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, recurrent malignancy 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 (P = 0.01), 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.
Type
Journal articleSubject
AdultAged
Antigens, CD27
B-Lymphocytes
Cross-Over Studies
Female
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Imatinib Mesylate
Male
Middle Aged
Prospective Studies
Rituximab
Sclerosis
Skin Diseases
Young Adult
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https://hdl.handle.net/10161/12562Published Version (Please cite this version)
10.1158/1078-0432.CCR-15-1443Publication Info
Arai, Sally; Pidala, Joseph; Pusic, Iskra; Chai, Xiaoyu; Jaglowski, Samantha; Khera,
Nandita; ... Flowers, Mary ED (2016). A Randomized Phase II Crossover Study of Imatinib or Rituximab for Cutaneous Sclerosis
after Hematopoietic Cell Transplantation. Clin Cancer Res, 22(2). pp. 319-327. 10.1158/1078-0432.CCR-15-1443. Retrieved from https://hdl.handle.net/10161/12562.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Stefanie Sarantopoulos
Professor of Medicine

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