Acalabrutinib targets activated BTK in macrophages and was associated with reduced inflammation and clinical improvement in COVID-19.

CD19-directed chimerical antigen receptor T-cell (CAR-T) products have gained US Food and Drug Administration approval for systemic large B-cell lymphoma. Because of concerns about potential immune cell-associated neurotoxicity syndrome (ICANS), patients with primary central nervous system (CNS) lymphoma (PCNSL) were excluded from all pivotal CAR-T studies. We conducted a phase 1/2 clinical trial of tisagenlecleucel in a highly refractory patients with PCNSL and significant unmet medical need. Here, we present results of 12 relapsed patients with PCNSL who were treated with tisagenlecleucel and followed for a median time of 12.2 months (range, 3.64-23.5). Grade 1 cytokine release syndrome was observed in 7/12 patients (58.3%), low-grade ICANS in 5/12 (41.6%) patients, and only 1 patient experienced grade 3 ICANS. Seven of 12 patients (58.3%) demonstrated response, including a complete response in 6/12 patients (50%). There were no treatment-related deaths. Three patients had ongoing complete remission at data cutoff. Tisagenlecleucel expanded in the peripheral blood and trafficked to the CNS. Exploratory analysis identified T-cell, CAR T, and macrophage gene signatures in cerebrospinal fluid following infusion when compared with baseline. Overall, tisagenlecleucel was well tolerated and resulted in a sustained remission in 3/7 (42.9%) of initial responders. These data suggest that tisagenlecleucel is safe and effective in this highly refractory patient population. This trial was registered at www.clinicaltrials.gov as #NCT02445248.

Lymphomatoid granulomatosis (LYG) is a very rare Epstein-Barr virus (EBV)-driven lymphoproliferative disease. The atypical lymphoid cells directly accumulate within affected tissues and clinically present in the form of infiltrative lesions. It is usually a progressive disorder that virtually always involves the lung and characteristically presents as bilateral pulmonary nodules. Other commonly affected organ systems include the skin, central nervous system, and kidneys. The rareness of LYG in conjunction with its nonspecific presentation contributes to delays in diagnosis in many situations. Pathologically, it is characterized by the presence of an angiocentric and angiodestructive accumulation of varying numbers of T cells with varying numbers of atypical clonal EBV-positive B cells in a polymorphous inflammatory background. It can be subclassified using a grading system based on the number of EBV-positive large B-cell malignant cells, which is critical in selecting appropriate management strategies. Lower-grade LYG occasionally undergoes spontaneous remission and is best managed with strategies designed to enhance the host’s underlying immune system, whereas high-grade LYG is best managed by combination chemoimmunotherapy but has inferior outcomes. Lymphomatoid granulomatosis can lead to progressive pulmonary failure, central nervous system disease, or progression to overt EBV-positive lymphoma without appropriate recognition and management. Improvements in the modern understanding of the biology of LYG, particularly the precise role of EBV in its pathogenesis, offer promise in the development of improved management strategies.

Burkitt’s lymphoma is a rapidly proliferating lymphoma of germinal-center B cells. Most patients are cured with chemotherapy and prevention of tumor lysis. Relapse and CNS involvement carry a poor prognosis.