Second primary malignancies were reported in 536 of 12 394 (4.3%) adverse event reports following chimeric antigen receptor T-cell therapies in the Food and Drug Administration Adverse Event Reporting System. Myeloid and T-cell neoplasms were disproportionately more frequently reported, warranting further follow-up.

Data addressing prognostication in patients with HIV related Burkitt lymphoma (HIV-BL) currently treated remain scarce. We present an international analysis of 249 (United States: 140; United Kingdom: 109) patients with HIV-BL treated from 2008 to 2019 aiming to identify prognostic factors and outcomes. With a median follow up of 4.5 years, the 3-year progression-free survival (PFS) and overall survival (OS) were 61% (95% confidence interval [CI] 55% to 67%) and 66% (95%CI 59% to 71%), respectively, with similar results in both countries. Patients with baseline central nervous system (CNS) involvement had shorter 3-year PFS (36%) compared to patients without CNS involvement (69%; P < .001) independent of frontline treatment. The incidence of CNS recurrence at 3 years across all treatments was 11% with a higher incidence observed after dose-adjusted infusional etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide (DA-EPOCH) (subdistribution hazard ratio: 2.52; P = .03 vs other regimens) without difference by CD4 count 100/mm3. In multivariate models, factors independently associated with inferior PFS were Eastern Cooperative Oncology Group (ECOG) performance status 2-4 (hazard ratio [HR] 1.87; P = .007), baseline CNS involvement (HR 1.70; P = .023), lactate dehydrogenase >5 upper limit of normal (HR 2.09; P < .001); and >1 extranodal sites (HR 1.58; P = .043). The same variables were significant in multivariate models for OS. Adjusting for these prognostic factors, treatment with cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate, ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) was associated with longer PFS (adjusted HR [aHR] 0.45; P = .005) and OS (aHR 0.44; P = .007). Remarkably, HIV features no longer influence prognosis in contemporaneously treated HIV-BL.

The gut microbiome is increasingly being recognized as an important immunologic environment, with direct links to the host immune system. The scale of the gut microbiome’s genomic repertoire extends the capacity of its host’s genome by providing additional metabolic output, and the close communication between gut microbiota and mucosal immune cells provides a continued opportunity for immune education. The relationship between the gut microbiome and the host immune system has important implications for oncologic disease, including lymphoma, a malignancy derived from within the immune system itself. In this review, we explore past and recent discoveries describing the role that bacterial populations play in lymphomagenesis, diagnosis, and therapy. We highlight key relationships within the gut microbiome-immune-oncology axis that present exciting opportunities for directed interventions intended to shape the microbiome for therapeutic effect. We conclude with a limited summary of active clinical trials targeting the microbiome in hematologic malignancies, along with future directions on gut microbiome investigations within lymphoid malignancies.

The gut microbiome is an important feature of host immunity with associations to hematologic malignancies and cellular therapy. We evaluated the gut microbiome and dietary intake in patients with multiple myeloma undergoing autologous stem cell transplantation. Thirty patients were enrolled, and samples were collected at four timepoints: pre-transplant, engraftment, day +100 (D + 100), and 9–12 months post-transplant. Microbiome analysis demonstrated a loss of alpha diversity at the engraftment timepoint driven by decreases in Blautia, Ruminococcus, and Faecalibacterium genera and related to intravenous antibiotic exposure. Higher fiber intake was associated with increased relative abundance of Blautia at the pre-transplant timepoint. Lower alpha diversity at engraftment was associated with a partial response to therapy compared with complete response (CR) or very good partial response (VGPR) (CR/VGPR vs. PR, p < 0.05). We conclude that loss of bacterial diversity at engraftment may be associated with impaired response to stem cell transplantation in multiple myeloma.

Primary CNS lymphoma (PCNSL) is a rare lymphoma representing 3% of CNS malignancies. The diagnosis is complicated by the unique risks associated with brain biopsy, and the treatment is similarly complicated by the restriction of effective therapeutics able to cross the blood-brain barrier. Currently, the majority of individuals diagnosed with this disease are immunocompetent although immune deficiency related to HIV or immunosuppressive therapy remains an important risk factor. Improvements in both frontline therapy and consolidation options, including the use of hematopoietic stem-cell transplantation, have translated to improved survival. Unfortunately, patients experiencing relapsed or refractory disease often fare poorly. Here, we review key clinical, pathologic, and therapeutic aspects of PCNSL and highlight challenging clinical scenarios that may be encountered by the treating oncologist.