Incidence, characteristics and outcomes in relapsed and refractory CD20+ PTLD: An institutional retrospective cohort study.

e19078 Background: Post-transplant lymphoproliferative disorder (PTLD) is a malignancy with significant morbidity and mortality after solid organ transplant (SOT). Frontline treatment of CD20+ PTLD is well established; however, there is a lack of data on the treatment of relapsed/refractory (R/R) PTLD, especially in the era of novel therapies approved since 2017 for diffuse large B-cell lymphoma. Methods: We conducted a single institution retrospective study of adult SOT patients with CD20+ PTLD. Inclusion criteria were age ≥18 and use of an adult regimen that included rituximab for frontline therapy. Baseline and pathologic characteristics, frontline and subsequent treatments, response rates, and toxicities were collected. Results: 71 cases of CD20+ PTLD were diagnosed between 01/01/2012 to 12/31/2022. The median age at diagnosis was 46. SOTs included kidney (46.5%), liver (21.1%), lung (16.9%), heart (14.1%), and pancreas (1.4%). Pathologically, 47 cases were monomorphic (12 germinal center B-cell-like [GCB] subtype, 26 non-GCB subtype, 9 cases indeterminate), 12 were polymorphic, 2 were non-destructive, and 10 were unclassified. 38 cases (53.5%) were Epstein-Barr virus positive. Frontline treatments included rituximab followed by R-CHOP (38.0%), rituximab monotherapy (16.9%), R-EPOCH (4.2%), and R-miniCHOP (2.8%). Toxicities included acute kidney injury (21.1%) and perforation (9.8%) and rejection (7%). The median overall survival (OS) was 62 months. 21 (29.6%) patients relapsed (N = 13) or were refractory (N = 8) to frontline treatment. Median time to relapse was 12.0 months. Systemic treatments included RCHOP, R-miniCHOP, RICE, R-Gemcitabine and oxaliplatin (R-GemOx), lenalidomide/tafasitamab (len/tafa), and R-ibrutinib with an overall response rate (ORR) of 72.2% in the second line setting; 50% of patients required dose reductions. Median OS was 17 months. Progression-free survival (PFS) was 4.5 months. The. ORR, median PFS and OS among those who received novel therapy (N=3) was 100%, 4.4 months, and not reached compared to 66.7%, 8 months, and 4.6 months with traditional cytotoxic therapy (N=15), respectively. 6 patients received a third line of therapy, which included polatuzumab-BR, CAR-T cell therapy, R-GemOx, len/tafa, and loncastuximab. ORR was 80%. 33% of patients required dose reductions. At data cutoff, 2 patients who received a third line of therapy were alive with stable disease on therapy. Causes of death in third line treatment included perforation (N=1), COVID (N = 1), fungemia (N=1), and cardiac arrest likely unrelated to PTLD (N = 1). 3 patients who died had active PTLD at time of death. No patients experienced graft rejection during treatment for R/R PTLD. Conclusions: R/R CD20+ PTLD after SOT remains a therapeutic challenge. Better understanding of cytotoxic versus novel therapies can help guide clinical decision making.