Post‐transplant lymphoproliferative disorder: Update on treatment and novel therapies

Abstract

Post-transplant lymphoproliferative disorder (PTLD) is rare and heterogeneous lymphoid proliferations that occur as a result of immunosuppression following solid organ transplant (SOT) and haematopoietic stem cell transplant (HSCT) with the majority being driven by EBV. Although some histologies are similar to lymphoid neoplasms seen in immunocompetent patients, treatment of PTLD may be different due to difference in pathobiology and higher risk of treatment complications. The most common treatment approach in SOT PTLD after failing immunosuppression reduction (RIS) takes into consideration a risk-stratified sequential algorithm with rituximab +/− chemotherapy based on phase 2 studies. In HSCT PTLD, RIS alone and chemotherapy are usually ineffective making rituximab +/− RIS as the gold standard of frontline treatment. In this review, we give an update on the treatment of PTLD beyond RIS. We highlight the most recent studies that attempted to incorporate more aggressive chemotherapy regimens and novel treatments into the traditional risk-stratified sequential approach. We also discuss the role of EBV-cytotoxic T lymphocytes in treatment of EBV-driven PTLD. Other novel agents with potential role in PTLD will be discussed in addition to the challenges that could arise with chimeric antigen receptor T-cell therapy and immune checkpoint inhibitors in this population.

Diverse and reprogrammable mechanisms of malignant cell transformation in lymphocytes: pathogenetic insights and translational implications

“…Recent study ( 59 ) identified in EBV-positive DLBCL relatively frequent mutations of SOCS1 , NOTCH2 , and NOTCH1 genes, suggesting that these mutated genes may have a pathogenic role in this type of lymphoid malignancy. While current therapies for in transplant patients affected by the EBV-driven lymphoproliferative disorders typically include tempering immunosuppressive regimens, often combined with CD20-targeting immunotherapy, or multiagent immunochemotherapy ( 60 ), the conceptually most advanced clinical trials focus on immunotherapy with EBV-detecting cytotoxic T cells ( 61 ) LMP-targeting CAR T cells ( 62 ), or anti-EBV vaccines ( 62 ).…”

Current Perspectives on the Management of Herpesvirus Infections in Solid Organ Transplant Recipients

“…The risk of lymphoproliferative disease is 12-fold higher in KTR compared with a matched non-transplant population [ 73 ]. PTLD is associated with EBV in >80% cases in Europe and United States [ 74 , 75 ]. The negative EBV serostatus of the recipient is the greatest risk factor of EBV-induced PTLD, since 90% of early onset PTLD occurred in seronegative recipients and mostly in the first year post-transplantation [ 76 ].…”

Epstein–Barr virus‐associated lymphomas decoded

“…Another approach involving prophylactic infusion of donor EBV‐specific CTL in high‐risk HSCT patients has been shown to be feasible and safe and is likely to be effective 61 . For further information, a recent update on novel therapies in PTLD is recommended 62 …”