Treatment Modalities Effect on Outcome in Post-Transplant Lymphoproliferative Disorder

Introduction: Post-transplant lymphoproliferative disorder (PTLD) is a common malignancy after solid organ transplant (SOT) with the incidence being as high as 25%. Given the heterogeneity of PTLD and the complexity of immunosuppressed patients, there is no standard up-front treatment regimen for PTLD. The rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH) regimen has been utilized at our facility (CUMC) because of the similarities between AIDS associated diffuse large B-cell lymphoma and PTLD given that they both are associated with impaired T-cell function. Those treated with R-EPOCH were treated according to the AIDS malignancy protocol NCT00049036 with cytoxan starting at 187 mg/m2. The other chemotherapy agents of this regimen were adjusted based on organ function in order to improve tolerability. The aim of this study was to evaluate treatment options for PTLD, including this strategy and others, and to determine overall outcome.

Methods: This was a retrospective study that reviewed patients at a single, large academic center who developed PTLD after SOT. Data was collected on PTLD patients (>18 years) from 2004 to 2021. A total of 122 patients met the inclusion criteria. Data included PTLD diagnosis date, histopathological morphology, tumor markers, treatments received, treatment outcomes, and mortality. Fisher’s exact test or chi-squared test were used to compare categorical variables, and Kaplan-Meier estimate was used to determine overall survival.

Results: Of the 122 PTLD patients reviewed, 59.0% received R-EPOCH therapy, 9.8% received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy, 13.9% received rituximab monotherapy, 1.6% received brentuximab/rituximab, and 15.6% received various other chemotherapy combinations.

There was a median follow up time of 2.58 years Across the entire patient population, 58.2% remained in complete remission, 26.2% progressed, and 15.6% died while on therapy. Of the patients treated with R-EPOCH, 23.6% progressed, while 41.7% of patients treated with R-CHOP progressed, 17.7% of patients treated with rituximab monotherapy progressed, 0% of patients treated with brentuximab/rituximab progressed, and 36.8% treated with other chemotherapy regimens progressed (p=0.011). Patients who relapsed were treated with salvage chemotherapy (56.3%), stem cell transplant (21.8%), CAR-T (6.3%), or no further therapy (15.6%).

Mortality rates were similar for EBV-positive (45.5%) and EBV-negative (45.9%) PTLD and there was no statistical difference by histopathological morphology (including monomorphic and polymorphic cases), CD30 positivity, or CD138 positivity. The 2-year overall survival (OS) was 0.761 (SE=0.052, 95% confidence interval 0.665-0.871) for those who received R-EPOCH and 0.417 (SE=0.142, 95% confidence interval 0.213-0.814) for those who received R-CHOP (Figure 1).

Conclusions: This retrospective analysis shows that dose adjusted R-EPOCH is an effective treatment in PTLD patients. Those treated with R-EPOCH generally have lower mortality rates, than those treated with R-CHOP or rituximab monotherapy, however there were small numbers of those receiving R-CHOP or rituximab monotherapy. There are limitations to this analysis as often patients with more aggressive disease, such as monomorphic PTLD, are treated with EPOCH therapy. Also, those with additional medical co-morbidities, who are unstable, or have limited disease may have only received rituximab monotherapy, thus skewing the results. More importantly, this data demonstrates the poor survival outcomes in PTLD compared to other large B-cell lymphoma and highlights the necessity of evaluation of further treatment options. Future multi-institutional studies are needed to allow for potential comparison of treatment strategies.