Purpose The Sequential Treatment of CD20-Positive Posttransplant
Lymphoproliferative Disorder (PTLD-1) trial ( ClinicalTrials.gov identifier, NCT01458548) established sequential treatment with four cycles of
rituximab followed by four cycles of
cyclophosphamide,
doxorubicin,
vincristine, and
prednisone (CHOP)
chemotherapy as a standard in the management of post-transplant
lymphoproliferative disorder (PTLD) and identified response to
rituximab induction as a prognostic factor for overall survival. We hypothesized that
rituximab consolidation might be sufficient treatment for patients with a complete response after
rituximab induction. Patients and Methods In this prospective, international, multicenter phase II trial, 152 treatment-naive adult solid organ transplant recipients, with CD20+ PTLD unresponsive to immunosuppression reduction, were treated with four weekly doses of
rituximab induction. After restaging, complete responders continued with four courses of
rituximab consolidation every 21 days; all others received four courses of
rituximab plus CHOP
chemotherapy every 21 days. The primary end point was treatment efficacy measured as the response rate in patients who completed
therapy and the response duration in those who completed
therapy and responded. Secondary end points were frequency of
infections, treatment-related mortality, and overall survival in the intention-to-treat population. Results One hundred eleven of 126 patients had a complete or partial response (88%; 95% CI, 81% to 93%), of whom 88 had a complete response (70%; 95% CI, 61% to 77%). Median response duration was not reached. The 3-year estimate was 82% (95% CI, 74% to 90%). Median overall survival was 6.6 years (95% CI, 5.5 to 7.6 years). The frequency of grade 3 or 4
infections and of treatment-related mortality was 34% (95% CI, 27% to 42%) and 8% (95% CI, 5% to 14%), respectively. Response to
rituximab induction remained a prognostic factor for overall survival despite treatment stratification. Conclusion In B-cell PTLD, treatment stratification into
rituximab or
rituximab plus CHOP consolidation on the basis of response to
rituximab induction is feasible, safe, and effective.