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Background: Cutaneous sclerosis (CS) occurs in 20% of patients (pts) with chronic graft-versus-host disease (cGVHD) and can severely compromise patient mobility and quality of life.
Methods: Prospective, multi-center, randomized, two-arm phase II crossover trial of imatinib (200 mg daily by mouth, provided by Novartis) and rituximab (375 mg/m2 intravenously weekly x 4 doses, repeatable after 3 month, provided by Genentech) for treatment of CS at 11 institutions within the Chronic GVHD Consortium (NCT01309997). CS was defined as sclerotic skin, morphea, myofascial involvement or joint contractures diagnosed within the past 18 months (a score of ≥2 in any area on the Vienna Skin Score (VSS), or a score of 5 or less at the shoulders, elbows, or wrists, or a score of 3 or less at the ankles on the photographic range of motion (P-ROM)). The primary endpoint was the significant clinical response (SCR) rate at 6 months, defined as a 2 or more point improvement on the VSS without worsening elsewhere or a 1-2 point improvement in the P-ROM scale without worsening elsewhere. Crossover was allowed at 6 months if CS did not improve, or earlier for CS progression or drug intolerance. Treatment success was defined as achievement of SCR at 6 months without crossing over to the second medication, recurrence of malignancy or death. With 37 pts per arm, SCR +/- 15% could be estimated.
Results: 72 pts were enrolled between March 2011 and June 2014, 35 randomized to imatinib and 37 to rituximab. The median age was 56 years (range 19-77), 44% were female, and all had organs other than skin involved with chronic GVHD at study enrollment. The median time from cGVHD onset to study enrollment was 1.0 year (range 0-3.8). 64 pts are evaluable for the primary endpoint; 8 have less than 6 months of followup. SCR was observed in 10/31 (32%) pts randomized to imatinib and 7/33 (21%) randomized to rituximab. Among SCR pts, 4 imatinib and 3 rituximab pts crossed over due to clinician-perceived lack of response despite SCR. Treatment success occurred for 6 (19%) on the imatinib arm and 4 (12%) on the rituximab arm.
Conclusion: SCR based on stringent objective improvement in physical findings was seen in <35% at 6-months after initial treatment with either imatinib or rituximab for CS, but treatment success was <20%. These results support the need for new therapies for CS.
