Faculty Collaboration Database

A Randomized Phase II Crossover Study of Imatinib or Rituximab for Cutaneous Sclerosis after Hematopoietic Cell Transplantation. Clin Cancer Res 2016 Jan 15;22(2):319-27

Date

09/18/2015

Pubmed ID

26378033

Pubmed Central ID

PMC4715914

DOI

10.1158/1078-0432.CCR-15-1443

Scopus ID

2-s2.0-84958983532 (requires institutional sign-in at Scopus site)   62 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: 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.

Author List

Arai S, Pidala J, Pusic I, Chai X, Jaglowski S, Khera N, Palmer J, Chen GL, Jagasia MH, Mayer SA, Wood WA, Green M, Hyun TS, Inamoto Y, Storer BE, Miklos DB, Shulman HM, Martin PJ, Sarantopoulos S, Lee SJ, Flowers ME

Author

Samantha M. Jaglowski MD, MPH Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
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
Tumor Necrosis Factor Receptor Superfamily, Member 7
Young Adult