CONSIDER CHARTING A DIFFERENT COURSE FOR EBV+ PTLD
Current treatment guidelines
There are no EMA- or FDA-approved treatments for EBV+ PTLD.
In SOT recipients with CD20 positive disease and HCT recipients with EBV+ PTLD, data, expert opinion, and transplant-specific guidelines recommend response-stratified sequential therapy consisting of RIS and anti-CD20 monotherapy, followed by chemotherapy when necessary.1,2
Recommendations are inclusive of monomorphic PTLD.
Guidelines from the American Society of Transplantation (AST), European Conference on Infections in Leukemia (ECIL-6), and National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®)* all recognize response-stratified sequential therapy of RIS, anti-CD20 monotherapy, and chemotherapy.1-3
*NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
TRANSPLANT-SPECIFIC GUIDELINES FOR THE MANAGEMENT OF PTLD FOLLOWING SOT OR HCT1,2
Chemotherapy, with or without anti-CD20 therapy
PTLD following SOT
(AST IDCOP 2019)
Chemotherapy with anti-CD20 therapy in patients with CD20 positive PTLD who have progressive disease after anti-CD20 monotherapy and are able to tolerate therapy
Chemotherapy alone in CD20 negative B-cell PTLD, T-cell PTLD, and Hodgkin and Burkitt lymphomas
PTLD following HCT
Chemotherapy, with or without anti-CD20 therapy, after lack of response to anti-CD20 monotherapy
Limited data on chemotherapy for PTLD after HCT and only recommended for relapsing/refractory cases
RECOMMENDATIONS ARE INCLUSIVE OF MONOMORPHIC PTLD.
EVIDENCE FOR RESPONSE-STRATIFIED SEQUENTIAL THERAPY CONSISTING OF RIS AND ANTI-CD20 MONOTHERAPY, FOLLOWED BY CHEMOTHERAPY WHEN NECESSARY2,4-6
In a large prospective trial of 152 patients with PTLD following SOT, of which 85% had monomorphic disease, 25% of patients achieved remission without chemotherapy, with complete response to anti-CD20 monotherapy predicting survival. Similar overall survival was observed when compared to a cohort of patients who all received chemotherapy after anti-CD20 monotherapy.4
In a multicenter retrospective study of 101 SOT patients with PTLD comparing anti-CD20 monotherapy with chemotherapy, 61% of patients treated up-front with anti-CD20 monotherapy achieved long-term remission without any additional therapy with a median follow-up of 25 months.5
In a retrospective cohort of 168 adult SOT patients (of which 96% had monomorphic disease), no difference in overall survival for patients treated with anti-CD20 primary strategy versus upfront anti-CD20 plus chemotherapy was observed. Anti-CD20 primary cohorts included patients who received only anti-CD20 and patients who received only anti-CD20 then sequential anti-CD20 plus chemotherapy.6
When used after initial anti-CD20 treatment in patients who are refractory or fail treatment, adding chemotherapy can be efficacious for SOT recipients with PTLD.4 While not all PTLD patients following SOT respond to initial anti-CD20 monotherapy, reserving chemotherapy for those who fail initial anti-CD20 monotherapy has not been shown to negatively impact survival.4,5
Per transplant-specific guidelines, chemotherapy for patients with EBV+ PTLD after HCT is not recommended first-line due to poor tolerability in HCT patients and the risk of inducing neutropenia and graft failure. Chemotherapy for EBV+ PTLD is, therefore, restricted to refractory or relapsing cases.2
HIGHER RATES OF REPORTED TREATMENT-RELATED MORTALITY (TRM) HAVE BEEN OBSERVED IN IMMUNOCOMPROMISED PATIENTS WITH PTLD THAN IN PATIENTS WITH IMMUNOCOMPETENT LYMPHOMA4-8
TRM in PTLD (immunocompromised) patients
In a large prospective trial of 152 SOT recipients with PTLD who failed RIS, TRM was 13% for patients treated with sequential therapy of anti-CD20 monotherapy followed by chemotherapy, and 8% for patients treated with response-stratified sequential treatment of anti-CD20 monotherapy, followed by chemotherapy when necessary.4
In a multicenter retrospective study of 101 SOT recipients with PTLD initially treated with anti-CD20 monotherapy or chemotherapy, non–PTLD-related mortality within 12 months of therapy was 7% for both cohorts.5
In a retrospective cohort of 168 adult SOT recipients with PTLD initially treated with anti-CD20 primary therapy* or anti-CD20 therapy in combination with chemotherapy, TRM was 7% versus 7.5% respectively.6
*Anti-CD20 primary therapy is defined as anti-CD20 monotherapy or sequential use of anti-CD20 therapy and chemotherapy.
TRM in immunocompetent lymphoma
In a randomized controlled clinical trial of 399 previously untreated patients with diffuse large B-cell lymphoma (DLBCL), aged 60 to 80 years old, treated with a combination of chemotherapy and anti-CD20 therapy or chemotherapy alone, TRM was 2% (4/202) and 0.5% (1/197) respectively.7
In a randomized controlled clinical trial of 824 young DLBCL patients with good prognosis treated with either anti-CD20 therapy plus chemotherapy or chemotherapy alone, TRM was 1.7% (6/404) and 0.2% (1/403) respectively.8
LEARN MORE ABOUT THE USE OF ANTI-CD20 THERAPY
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1. Allen UD, Preiksaitis JK. Post-transplant lymphoproliferative disorders, Epstein-Barr virus infection, and disease in solid organ transplantation: guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13652. 2. Styczynski J, van der Velden W, Fox CP, et al. Management of Epstein-Barr virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines. Haematologica. 2016;101(7):803-811. 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.3.2021. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed April 21, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. 4. Trappe RU, Dierickx D, Zimmermann H, et al. Response to rituximab induction is a predictive marker in B-cell post-transplant lymphoproliferative disorder and allows successful stratification into rituximab or R-CHOP consolidation in an international, prospective, multicenter phase II trial. J Clin Oncol. 2017;35(5):536-543. 5. Burns DM, Clesham K, Hodgson YA, et al. Real-world outcomes with rituximab-based therapy for posttransplant lymphoproliferative disease arising after solid organ transplant. Transplantation. 2020;104(12):2582–2590. 6. Jain MD, Lam R, Liu Z, et al. Failure of rituximab is associated with a poor outcome in diffuse large B cell lymphoma-type post-transplant lymphoproliferative disorder. Br J Haematol. 2020;189(1):97-105. 7. Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(4):235-242. 8. Pfreundschuh M, Trümper L, Osterborg A, et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006;7(5):379-391. 9. Dierickx D, Habermann TM. Post-transplantation lymphoproliferative disorders in adults. N Eng J Med. 2018;378(6):549-562. 10. Trappe R, Oertel S, Leblond V, et al. Sequential treatment with rituximab followed by CHOP chemotherapy in adult B-cell post-transplant lymphoproliferative disorder (PTLD): the prospective international multicentre phase 2 PTLD-1 trial. Lancet Oncol. 2012;13(2):196-206.