CONSIDER CHARTING A DIFFERENT COURSE FOR EBV+ PTLD

Current treatment

There are no EMA- or FDA-approved treatments for EBV+ PTLD.

In SOT recipients with CD20 positive disease who have failed RIS and HCT recipients with EBV+ PTLD, data, expert opinion, and transplant-specific guidelines recommend initial treatment with anti-CD20 monotherapy, followed by chemotherapy when necessary.1,2

Recommendations are inclusive of monomorphic PTLD

PTLD Guidelines

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 initial treatment with anti-CD20 monotherapy with RIS, followed by chemotherapy when necessary.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

INITIAL TREATMENT AFTER FAILURE OF RIS

Anti-CD20 monotherapy

In patients with CD20 positive PTLD with progressive disease

downward arrow

SUBSEQUENT TREATMENT

Chemotherapy, with or without anti-CD20 therapy

  • 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 patients with CD20 negative B-cell PTLD, T-cell PTLD, and Hodgkin and Burkitt lymphomas

Select the links to read the source guidelines: AST Guidelines, ECIL-6 Guidelines1,2

GUIDELINES ARE INCLUSIVE OF MONOMORPHIC PTLD

PTLD Guidelines

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 risk-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

TREATMENT

Anti-CD20 monotherapy, with or without RIS after evaluation

Treatment Step

Initial treatment

PTLD following SOT
(AST IDCOP 2019)

In patients with CD20 positive PTLD with progressive disease after RIS

PTLD following HCT
(ECIL-6 2016)

Initial treatment or may be combined with RIS

TREATMENT

Chemotherapy, with or without anti-CD20 therapy

Treatment Step

Subsequent treatment

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
(ECIL-6 2016)

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

Select the links to read the source guidelines: AST Guidelines, ECIL-6 Guidelines1,2

RECOMMENDATIONS ARE INCLUSIVE OF MONOMORPHIC PTLD.

SOT RECIPIENTS WITH PTLD: EVIDENCE FOR INITIAL TREATMENT WITH ANTI-CD20 MONOTHERAPY WITH RIS AFTER FAILURE OF INITIAL TREATMENT, FOLLOWED BY CHEMOTHERAPY WHEN NECESSARY2,4-6

When used after initial anti-CD20 monotherapy 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

PTLD trial data - chemotherapy and monotherapy

HIGHER RATES OF REPORTED TREATMENT-RELATED MORTALITY (TRM) HAVE BEEN OBSERVED IN IMMUNOSUPPRESSED TRANSPLANT PATIENTS WITH PTLD THAN IN IMMUNOCOMPETENT PATIENTS WITH LYMPHOMA4-8

TRM in PTLD Immunosuppressed 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 risk-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 patients with 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

Response to Rituximab Induction is a Predictive Marker in B-Cell PTLD

RU Trappe, D Dierickx, H Zimmermann, et al

Response to Rituximab Induction Is a Predictive Marker in B-Cell Post-transplant Lymphoproliferative Disorder

Journal of Clinical Oncology
2017;35(5):563-543

Real-World Outcomes With Rituximab-based Therapy for PTLD

DM Burns, K Clesham, YA Hodgson, et al

Real-World Outcomes With Rituximab-based Therapy for Posttransplant Lymphoproliferative Disease Arising After Solid Organ Transplant

Transplantation
2020;104(12):2582-2590

Failure of Rituximab Is Associated With a Poor Outcome in Diffuse Large B Cell Lymphoma-type PTLD

MD Jain, R Lam, Z Liu, et al

Failure of Rituximab Is Associated With a Poor Outcome in Diffuse Large B Cell Lymphoma-type Post-transplant Lymphoproliferative Disorder

British Journal of Haematology
2020;189(1):97-105

GUIDELINES DO NOT RECOMMEND ANTIVIRALS AS A TREATMENT FOR EBV+ PTLD

Although antivirals have been considered for use in patients with EBV+ PTLD, there is limited clinical data to support their use and they are not recommended in guidelines.2

THE BOTTOM LINE

In SOT recipients with CD20 positive disease who have failed RIS and HCT recipients with EBV+ PTLD, data, expert opinion, and transplant-specific guidelines recommend initial treatment with anti-CD20 monotherapy, followed by chemotherapy when necessary.1,2

You might also be interested in these resources

The Role of Epstein-Barr Virus (EBV) in Lymphomagenesis

JI Cohen, CM Bollard, R Khanna, S Pittaluga

Current Understanding of the Role of Epstein-Barr Virus (EBV) in Lymphomagenesis

Leukemia & Lymphoma
2008;49(suppl 1):27-34

Dr Trappe
Reducing Immunosuppression
in PTLD
00:51
Dr Lim
RIS in Heart Transplant
Recipients
01:16

References

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. Dierickx D, Habermann TM. Post-transplantation lymphoproliferative disorders in adults. N Eng J Med. 2018;378(6):549-562.