Refractory Epstein-Barr Virus-Negative Diffuse Large B-Cell Lymphoma Post-Transplant Lymphoproliferative Disorder in a Renal Transplant Patient Treated With Bispecific Antibody Therapy

Sep 28, 2026

Post-transplant lymphoproliferative disorder (PTLD) is a rare complication after stem cell or organ transplantation and may be either Epstein-Barr virus (EBV)-positive or EBV-negative. Standard management combines reduction of immunosuppression with anti-CD20 therapy followed by chemotherapy, yet refractory disease still carries high mortality. Literature describes limited options, including stem cell transplant and CAR-T, with constrained success. This case reports progression of refractory EBV-negative PTLD after third-line treatment, bridged with glofitamab as a bispecific antibody.

LanguageEnglish

CategoryHealthcare

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Pages8

Reading Time20 min

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Abstract

Introduction

Case Report

Investigations

Case Report J Med Cases. 2026;17(1):1-8 Refractory Epstein-Barr Virus-Negative Diffuse Large B-Cell Lymphoma Post-Transplant Lymphoproliferative Disorder in a Renal Transplant Patient Treated With Bispecific Antibody Therapy Austin Frischa, d, Bobby Sea, Eric Martina, Haresh Manib, Stephen Medlinc, Zartash Gulc Abstract Post-transplant lymphoproliferative disorder (PTLD) is a rare disorder that can occur in both stem cell and organ transplant recipients. Most cases of PTLD arise from Epstein-Barr virus (EBV)-induced oncogenesis but it can be EBV-negative. The treatment algorithm involves reduction in immunosuppression combined with anti-CD20 antibody treatment followed by chemotherapy. Despite this, mortality is still high, and many patients have refractory disease. Refractory PTLD is challenging to treat, and the data on treatment are limited. Both stem cell transplant and chimeric antigen receptor T-cell (CAR-T) therapies have been described in case reports and small reviews, but success has been limited. Hence, there is a need for novel therapies and clinical trials to formulate better treatment plans. Here, we present a complex case of refractory EBV-negative PTLD that progressed on third-line treatment. Given the patient’s limited options, glofitamab, a bispecific antibody therapy, was initiated in attempt to bridge to CAR-T therapy. Unfortunately, the patient encountered multiple hospitalizations and eventually elected for hospice care not long after initiation of this fourth-line regimen began. Herein, we detail the diagnosis and treatment options for EBV-negative refractory PTLD with an in-depth literature review that highlights bispecific antibodies as a potential novel therapy. Keywords: DLBCL; PTLD; Transplant; Bispecific antibody; Lymphoma Introduction Post-transplant lymphoproliferative disorder (PTLD) is a Manuscript submitted August 9, 2025, accepted September 25, 2025 Published online October 10, 2025 aDepartment of Internal Medicine, Inova Fairfax Medical Center, Falls Church, VA, USA bDepartment of Pathology, Inova Fairfax Medical Center, Falls Church, VA, USA cInova Schar Cancer Center, Inova Fairfax Medical Center, Falls Church, VA, USA dCorresponding Author: Austin Frisch, Department of Internal Medicine, Inova Fairfax Hospital, Fairfax, VA, USA. Email: [afrischy2015@gmail.com](afrischy2015@gmail.com) doi: [https://doi.org/10.14740/jmc5186](https://doi.org/10.14740/jmc5186) rare malignancy that can occur after organ transplantation. PTLD incidence varies depending on which organ is transplanted and patients who receive multi-organ transplants are at the highest risk. Kidney transplants tend to have the lowest incidence of PTLD cases with 1.58 per 1,000 persons/ year and a 25-year cumulative PTLD incidence of roughly 3.3%[1, 2] . Immunosuppression (IS) and chronic viral infection, particularly Epstein-Barr virus (EBV), are the major risk factors for PTLD and the highest risk occurs within the first year of transplant [3]. This disease can present locally or advanced with the most common locations being gastrointestinal or lymph nodes and the most common symptoms being fever and weight loss. Most PTLD cases are EBV-positive (60-80%), while EBV-negative cases are extremely rare [4] . Treatment of PTLD includes cytotoxic chemotherapy, targeted antibody therapy, and reduction of IS. However, it is difficult to determine efficacy of these therapies leading to poor outcomes (overall survival 60%) due to the rarity and heterogeneity of this disease [5] . The standard of care for PTLD involves the reduction of IS by about 50% and treatment with an anti-CD20 monoclonal antibody such as rituximab or obinutuzumab. Chemotherapy regimens such as rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) can be used when PTLD are refractory to first-line therapies. Beyond this, exciting new research and clinical trials are underway testing the efficacy of bispecific ant

FAQs

What is post-transplant lymphoproliferative disorder (PTLD), and why can it be difficult to treat?

PTLD is a rare malignancy after transplantation that can occur with or without EBV. Refractory disease has limited treatment data and high mortality, making management challenging.

What treatment strategy is described for PTLD in general, and what is the standard approach?

The approach includes reducing immunosuppression and using anti-CD20 antibody therapy, often followed by chemotherapy such as R-CHOP for refractory cases.

How was the patient with EBV-negative refractory PTLD treated in this case report?

After progression on third-line therapy, the patient was started on glofitamab, a bispecific antibody therapy, with the intent to bridge to CAR-T. The patient later experienced multiple hospitalizations and chose hospice care.

Sep 28, 2026

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