Retrospective Evaluation of R-EPOCH in the Frontline Treatment of Adult PTLD Patients Following Solid Organ Transplant

• In a single institution retrospective study, B-cell PTLD patients treated with dose-modified R-EPOCH experienced a mOS of 6.4 years.

• Adverse events seen with R-EPOCH appear similar to those with R-CHOP, but with lower treatment related mortality.

Posttransplant lymphoproliferative disorders (PTLD) are rare complications of solid organ transplantation which carry significant morbidity and mortality. Phase II trials which utilized sequential rituximab followed by rituximab, 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 where dose-modified rituximab, 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 rituximab 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% for DM-R-EPOCH and 88% each for R-CHOP. Treatment related mortality for DM-R-EPOCH and R-CHOP treated patients was 4.7% and 25%, respectively. The median number of cycles of DM-R-EPOCH was 6 and between 73-89% 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 due to 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.