Failure of rituximab is associated with a poor outcome in diffuse large B cell lymphoma‐type post‐transplant lymphoproliferative disorder

Abstract

Summary Post‐transplant lymphoproliferative disorder (PTLD) may arise after solid organ transplantation, and the most common subtype resembles diffuse large B cell lymphoma (DLBCL). In DLBCL‐type PTLD, the anti‐CD20 antibody rituximab (R) may be combined with chemotherapy (R‐CHOP) or use a strategy (R‐primary; similar to the PTLD‐1 clinical trial) consisting of induction with four weekly doses of R‐alone, without any chemotherapy or sequential R‐CHOP follow‐up. Here we report on a multicentre retrospective cohort of solid organ transplant patients with DLBCL‐type PTLD that were treated with R. In 168 adults, two‐year overall survival (OS) was 63·7% [95% CI (confidence interval) 56·6–71·7%]. No difference in OS was observed, whether patients were treated with R‐CHOP versus the R‐primary strategy. In the 109 patients treated with R‐primary, multivariate analysis found that baseline IPI score and the response to R‐induction predicted OS. Patients who responded to R‐induction had durable remissions without the addition of chemotherapy. Conversely, of the 46 patients who had stable or progressive disease after R‐induction (R‐failure), those who received R‐CHOP had an only marginally improved outcome, with a two‐year OS of 45% (23·1–65·3%) vs. no R‐CHOP at 32% (14·7–49·8%). In real‐world patients, R‐failure and high IPI scores predict a poor outcome in DLBCL‐type PTLD.

Incidence and outcomes of post‐transplant lymphoproliferative disease after 5365 solid‐organ transplants over a 20‐year period at two UK transplant centres

“…A recent ANZDATA study 12 showed an excess risk of death in kidney‐transplant recipients with PTLD, particularly in the first two years after diagnosis which fits with our landmark analysis. The number of deaths in our study (39/90, 43%, median follow‐up 5.9 years) is in keeping with a Canadian study restricted to DLBCL‐type PTLD treated with rituximab/R‐CHOP (82/168, 48%, median follow‐up 2.4 years) 13 . However, a larger proportion of patients died due to non‐lymphoma causes in our study (34% compared with 22% in the Canadian study).…”

“…The number of deaths in our study (39/90, 43%, median follow-up 5.9 years) is in keeping with a Canadian study restricted to DLBCL-type PTLD treated with rituximab/R-CHOP (82/168, 48%, median follow-up 2.4 years). 13 However, a larger proportion of patients died due to non-lymphoma causes in our study (34% compared with 22% in the Canadian study). Burns et al reported a 12-month non-PTLD mortality of 7%, 9 compared to 25% and 17% in our R-Chemo and R-Mono groups respectively.…”

Multicenter study of pediatric Epstein‐Barr virus–negative monomorphic post solid organ transplant lymphoproliferative disorders

“…8 In two recent international, prospective, multicenter adult PTLD trials, more than half of the patients (53% and 62%) had EBV(−) PTLD. 15,23 In another large study, EBV(−) cases markedly increased over time from 10% (1990-1995) to 48% (2008-2013). 6 Whether the same trend has occurred in pediatric EBV(−) PTLD is unknown.…”

Baseline 18F-FDG Metabolic Tumor Volume Predicts Response to Rituximab Induction in Post-transplant Lymphoproliferative Disorders: A Multi-institutional Retrospective Study

“…End of treatment CR were 76.3% (29/38) and 81.8% (18/22), respectively. Jain et al 20 used a similar protocol on 109 patients (25% of PR patients treated by chemotherapy) and reported an R-induction CR rate of 43%.…”