Retrospective evaluation of R-EPOCH in the frontline treatment of adult patients with PTLD after solid organ transplant

Abstract

Posttransplant lymphoproliferative disorders (PTLD) are rare complications of solid organ transplantation, which carry significant morbidity and mortality. Phase 2 trials that use sequential rituximab (R) followed by R, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) have become an acceptable approach for B-cell PTLD, although it carries a high risk of treatment-related mortality (up to 11%). Many aspects of B-cell PTLD biology and patient characteristics parallel AIDS-related lymphomas in which dose-modified R, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DM-R-EPOCH) has been demonstrated to be highly efficacious and safe. In this single-institution retrospective study of (N = 101) adult transplant recipients with B-cell PTLD, 65 received DM-R-EPOCH, 8 received R-CHOP, and 17 received R monotherapy. Median progression-free and overall survival was 4.4 years and 6.4 years, respectively, for DM-R-EPOCH and 1 year and 1.1 years, respectively, for R-CHOP. Rates of neutropenia and infection were 70% and 77%, respectively, for DM-R-EPOCH, and 88% each for R-CHOP. Treatment-related mortality for patients treated with DM-R-EPOCH and R-CHOP was 4.7% and 25%, respectively. The median number of cycles of DM-R-EPOCH was 6, and between 73% and 89% of patients received a relative dose intensity of ≥80% for cyclophosphamide, etoposide, and doxorubicin. The relative dose intensity of vincristine was <80% in 56% of patients because of frequent omission for gastrointestinal involvement of PTLD. Collectively, these data suggest that DM-R-EPOCH does not lead to excessive toxicity in patients with B-cell PTLD and support the need for further prospective clinical studies.