Chimeric antigen receptor (CAR) T cells targeting CD19 have emerged as a leading engineered T-cell therapy for relapsed/refractory B-cell non-Hodgkin lymphoma. The phase 1/2 clinical trials that led to US Food and Drug Administration approval excluded patients with central nervous system (CNS) involvement, due to strict eligibility criteria. Here, we report on our institutional experience with 8 secondary CNS lymphoma patients treated with commercial tisagenlecleucel. No patient experienced greater than grade 1 neurotoxicity, and no patient required tocilizumab or steroids for CAR T-cell–mediated toxicities. Biomarker analysis suggested CAR T-cell expansion, despite the absence of systemic disease, and early response assessments demonstrated activity of IV infused CAR T cells within the CNS space.

Autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed/refractory (RR) classical Hodgkin lymphoma (cHL) who respond to salvage chemotherapy. However, relapse after ASCT remains a frequent cause of treatment failure, with poor subsequent prognosis. Because cHL is uniquely vulnerable to programmed cell death-1 (PD-1) blockade, PD-1 blockade given as consolidation after ASCT could improve ASCT outcomes. We therefore conducted a multicohort phase 2 study of pembrolizumab in patients with RR cHL after ASCT, hypothesizing that it would improve the progression-free survival (PFS) at 18 months after ASCT (primary end point) from 60% to 80%. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 8 cycles, starting within 21 days of post-ASCT discharge. Thirty patients were treated on this study. The median age was 33 years, and 90% were high-risk by clinical criteria. Seventy-seven percent completed all 8 cycles. Toxicity was manageable, with 30% of patients experiencing at least 1 grade 3 or higher adverse event (AE), and 40% at least 1 grade 2 or higher immune-related AE. Two patients were lost to follow-up in complete remission at 12 months. The PFS at 18 months for the 28 evaluable patients was 82%, meeting the primary end point. The 18-month overall survival was 100%. In conclusion, pembrolizumab was successfully administered as post-ASCT consolidation in patients with RR cHL, and resulted in a promising PFS in a high-risk patient cohort, supporting the testing of this strategy in a randomized trial. This trial was registered at www.clinicaltrials.gov as #NCT02362997.

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Epstein-Barr virus (EBV) is a ubiquitous herpesvirus, affecting up to 90% of the population. EBV was first identified as an oncogenic virus in a Burkitt lymphoma cell line, though subsequently has been found to drive a variety of malignancies, including diffuse large B-cell lymphoma (DLBCL) and other lymphoma subtypes. EBV has a tropism for B-lymphocytes and has the unique ability to exist in a latent state, evading the host immune response. In cases of impaired cell mediated immunity, as in patients with advanced age or iatrogenic immune suppression, the virus is able to proliferate in an unregulated fashion, expressing viral antigens that predispose to transformation. EBV-positive DLBCL not otherwise specified, which has been included as a revised provisional entity in the 2016 WHO classification of lymphoid malignancies, is thought to commonly occur in older patients with immunosenescence. Similarly, it is well-established that iatrogenic immune suppression, occurring in both transplant and non-transplant settings, can predispose to EBV-driven lymphoproliferative disorders. EBV-positive lymphoproliferative disorders are heterogeneous, with variable clinical features and prognoses depending on the context in which they arise. While DLBCL is the most common subtype, other histologic variants, including Burkitt lymphoma, NK/T-cell lymphoma, and Hodgkin lymphoma can occur. Research aimed at understanding the underlying biology and disease prevention strategies in EBV-associated lymphoproliferative diseases are ongoing. Additionally, personalized treatment approaches, such as immunotherapy and adoptive T-cell therapies, have yielded encouraging results, though randomized trials are needed to further define optimal management.

Burkitt lymphoma (BL) is a highly aggressive, B-cell, non-Hodgkin lymphoma (NHL) categorized into endemic, sporadic and immunodeficiency-associated subtypes. BL has distinct pathologic and clinical features, characterized by rapidly progressive tumors with high rates of extranodal involvement. Next generation sequencing (NGS) analyses have further characterized the genomic landscape of BL and our understanding of disease pathogenesis, though these findings have yet to influence treatment. Although the majority of patients are cured with intensive combination chemotherapy, given the paucity of randomized trials, optimal therapy has not been defined. Furthermore, treatment for elderly patients, patients with central nervous system (CNS) involvement, or those with relapsed disease, remains an unmet need. In this review, we highlight the clinical, pathologic, and genomic features, as well as standard and emerging treatment options for adult patients with BL.