Posttransplant Rituximab Exposure and Risk of PTLD in Solid Organ Transplant Recipients with EBV DNAemia Open Access

• Rituximab treatment in solid organ transplant recipients with EBV DNAemia may be associated with a reduction in the rate of PTLD over time.

• Increasing EBV viral load, lung or multivisceral transplant, and high-risk serostatus were associated with higher rates of PTLD over time.

The association between Epstein-Barr Virus (EBV) DNAemia after solid organ transplantation (SOT) and posttransplant lymphoproliferative disorder (PTLD) is well described. Published data support preemptive rituximab for EBV DNAemia after bone marrow transplant. However, there is inadequate data to support any specific preemptive strategy for DNAemia after SOT. The goal of this single-center retrospective cohort study was to explore the association between posttransplant rituximab and development of PTLD in SOT recipients with EBV DNAemia. This study included 1386 patients with EBV DNAemia after SOT at Columbia University Irving Medical Center from 2008 to 2023. There were 129 patients who received rituximab for various indications (e.g. organ rejection, EBV DNAemia). Across all patients, 6% (82/1386) developed PTLD and the 5-year PTLD-free survival rate was 95%. In multivariable analysis, posttransplant rituximab exposure for any indication was independently associated with a reduced rate of PTLD over time as a time-independent (HR 0.16, p=0.011) but not time-dependent (HR 0.25, p=0.056) variable. When limiting the rituximab-exposed cohort to the 60 patients who received rituximab after documented EBV DNAemia time-independent (HR 0.25, p=0.06) and time-dependent (HR 0.43, p=0.2) rituximab exposure were not associated with PTLD-free survival. Higher EBV peak viral load, high-risk organ transplant type, and high-risk EBV serostatus were independently associated with increased rates of PTLD. This retrospective study suggests that posttransplant rituximab may reduce the rate of PTLD in SOT recipients. Prospective, randomized studies are needed to more rigorously determine the benefit of preemptive rituximab for the prevention of PTLD in patients with EBV DNAemia.