Ibrutinib is a Bruton tyrosine kinase inhibitor that is used for the treatment of lymphoid cancers, including chronic lymphocytic leukemia, Waldenström macroglobulinemia, and mantle cell lymphoma. Several case series have described opportunistic infections among ibrutinib recipients, but the full extent of these infections is unknown. We sought to determine the spectrum of serious infections associated with ibrutinib treatment. We reviewed the electronic medical records of patients with lymphoid cancer at Memorial Sloan Kettering Cancer Center who received ibrutinib during a 5-year period from 1 January 2012 to 31 December 2016. Serious infections were identified by review of the relevant microbiology, clinical laboratory, and radiology data. Risk factors for infection were determined by means of univariate and multivariate analyses. We analyzed findings in 378 patients with lymphoid cancer who received ibrutinib. The most common underlying cancers were chronic lymphocytic leukemia and mantle cell lymphoma. 84% of patients received ibrutinib as monotherapy. Serious infection developed in 43 patients (11.4%), primarily during the first year of ibrutinib treatment. Invasive bacterial infections developed in 23 (53.5%) of these patients, and invasive fungal infections (IFIs) in 16 (37.2%) .The majority of patients with IFIs during ibrutinib therapy (62.5%) lacked classic clinical risk factors for fungal infection (ie, neutropenia, lymphopenia, and receipt of corticosteroids). Infection resulted in death in 6 of the 43 patients (14%). Patients with lymphoid cancer receiving ibrutinib treatment are at risk for serious infections, including IFIs.

BCG is a live attenuated strain of Mycobacterium bovis that is primarily used as a vaccine against tuberculosis. In the past four decades, BCG has also been used for the treatment of non-muscle invasive bladder cancer (NMIBC). In patients with NMIBC, BCG reduces the risk of tumor recurrence and decreases the likelihood of progression to more invasive disease. Despite the long-term clinical experience with BCG, its mechanism of action is still being elucidated. Data from animal models and from human studies suggests that BCG activates both the innate and adaptive arms of the immune system eventually leading to tumor destruction. Herein, we review the current data regarding the mechanism of BCG and summarize the evidence for its clinical efficacy and recommended indications and clinical practice.

Significance: Bacillus Calmette–Guérin (BCG) therapy is one of the oldest tumor immunotherapies, but its mechanism remains unknown. Herein we show that BCG therapy induces tumor-specific T cell-dependent immunity that is predominantly mediated by CD4 T cells in a manner distinct from other tumor immunotherapies. These immunologic insights may allow investigation into biomarkers that could predict the efficacy of BCG in human cancer patients.

Summary: Bacterial pathogens rely on their DNA repair pathways to resist genomic damage inflicted by the host. DNA double‐strand breaks (DSBs) are especially threatening to bacterial viability. DSB repair by homologous recombination (HR) requires nucleases that resect DSB ends and a strand exchange protein that facilitates homology search. RecBCD and RecA perform these functions in Escherichia coli and constitute the major pathway of error‐free DSB repair. Mycobacteria, including the human pathogen M. tuberculosis, elaborate an additional error‐prone pathway of DSB repair via non‐homologous end‐joining (NHEJ) catalysed by Ku and DNA ligase D (LigD). Little is known about the relative contributions of HR and NHEJ to mycobacterial chromosome repair, the factors that dictate pathway choice, or the existence of additional DSB repair pathways. Here we demonstrate that Mycobacterium smegmatis has three DSB repair pathway options: HR, NHEJ and a novel mechanism of single‐strand annealing (SSA). Inactivation of NHEJ or SSA is compensated by elevated HR. We find that mycobacterial RecBCD does not participate in HR or confer resistance to ionizing radiation (IR), but is required for the RecA‐independent SSA pathway. In contrast, the mycobacterial helicase–nuclease AdnAB participates in the RecA‐dependent HR pathway, and is a major determinant of resistance to IR and oxidative DNA damage. These findings reveal distinctive features of mycobacterial DSB repair, most notably the dedication of the RecBCD and AdnAB helicase–nuclease machines to distinct repair pathways.

Nearly 100 years since it was first used in humans as a vaccine for tuberculosis, Bacillus Calmette–Guérin (BCG) has been suggested as a possible agent to prevent coronavirus disease 2019 (COVID-19). A number of studies are underway to investigate this possibility but — even if they prove effective — many questions will remain.

New York State had 180,458 cases of SARS-CoV-2 and 9385 reported deaths as of April 10 ^th , 2020. Patients with cancer comprised 8.4% of deceased individuals ¹ . Population-based studies from China and Italy suggested a higher COVID-19 death rate in patients with cancer ^2,3 , although there is a knowledge gap as to which aspects of cancer and its treatment confer risk of severe COVID-19 disease ⁴ . This information is critical to balance the competing safety considerations of reducing SARS-CoV-2 exposure and cancer treatment continuation. Since March 10 ^th , 2020 Memorial Sloan Kettering Cancer Center (MSKCC) performed diagnostic testing for SARS-CoV-2 in symptomatic patients. Overall, 40% out of 423 patients with cancer were hospitalized for COVID-19 illness, 20% developed severe respiratory illness, including 9% that required mechanical ventilation, and 9% that died. On multivariate analysis, age ≥ 65 years and treatment with immune checkpoint inhibitors (ICI) within 90 days were predictors for hospitalization and severe disease, while receipt of chemotherapy within 30 days and major surgery were not. Overall, COVID-19 illness is associated with higher rates of hospitalization and severe outcomes in patients with cancer. Association between ICI and COVID-19 outcomes will need interrogation in tumor-specific cohorts.