The NCCN Guidelines for Management of Immunotherapy-Related Toxicities provide interdisciplinary guidance on the management of immune-related adverse events (irAEs) resulting from cancer immunotherapy. These NCCN Guidelines Insights describe symptoms that may be caused by an irAE and should trigger further investigation, and summarize the NCCN Management of Immunotherapy-Related Toxicities Panel discussions for the 2020 update to the guidelines regarding immune checkpoint inhibitor–related diarrhea/colitis and cardiovascular irAEs.

Deep convolutional neural network (DCNN) models have been widely explored for skin disease diagnosis and some of them have achieved the diagnostic outcomes comparable or even superior to those of dermatologists. However, broad implementation of DCNN in skin disease detection is hindered by small size and data imbalance of the publically accessible skin lesion datasets. This paper proposes a novel single-model based strategy for classification of skin lesions on small and imbalanced datasets. First, various DCNNs are trained on different small and imbalanced datasets to verify that the models with moderate complexity outperform the larger models. Second, regularization DropOut and DropBlock are added to reduce overfitting and a Modified RandAugment augmentation strategy is proposed to deal with the defects of sample underrepresentation in the small dataset. Finally, a novel Multi-Weighted New Loss (MWNL) function and an end-to-end cumulative learning strategy (CLS) are introduced to overcome the challenge of uneven sample size and classification difficulty and to reduce the impact of abnormal samples on training. By combining Modified RandAugment, MWNL and CLS, our single DCNN model method achieved the classification accuracy comparable or superior to those of multiple ensembling models on different dermoscopic image datasets. Our study shows that this method is able to achieve a high classification performance at a low cost of computational resources and inference time, potentially suitable to implement in mobile devices for automated screening of skin lesions and many other malignancies in low resource settings.

Chronic graft-versus-host disease (cGVHD) is a life-threatening impediment to allogeneic hematopoietic stem cell transplantation, and current therapies do not completely prevent and/or treat cGVHD. CD4⁺ T cells and B cells mediate cGVHD; therefore, targeting these populations may inhibit cGVHD pathogenesis. Ibrutinib is an FDA-approved irreversible inhibitor of Bruton’s tyrosine kinase (BTK) and IL-2 inducible T cell kinase (ITK) that targets Th2 cells and B cells and produces durable remissions in B cell malignancies with minimal toxicity. Here, we evaluated whether ibrutinib could reverse established cGVHD in 2 complementary murine models, a model interrogating T cell–driven sclerodermatous cGVHD and an alloantibody-driven multiorgan system cGVHD model that induces bronchiolar obliterans (BO). In the T cell–mediated sclerodermatous cGVHD model, ibrutinib treatment delayed progression, improved survival, and ameliorated clinical and pathological manifestations. In the alloantibody-driven cGVHD model, ibrutinib treatment restored pulmonary function and reduced germinal center reactions and tissue immunoglobulin deposition. Animals lacking BTK and ITK did not develop cGVHD, indicating that these molecules are critical to cGVHD development. Furthermore, ibrutinib treatment reduced activation of T and B cells from patients with active cGVHD. Our data demonstrate that B cells and T cells drive cGVHD and suggest that ibrutinib has potential as a therapeutic agent, warranting consideration for cGVHD clinical trials.

Stevens-Johnson Syndrome/toxic epidermal necrolysis (SJS/TEN) is a spectrum of rare, severe mucocutaneous drug reaction associated with significant morbidity and mortality. Clinically, patients present with atypical targetoid lesions or generalized erythema progressing to full-thickness epidermal necrosis. Patients are classified by the extent of epidermal detachment, with SJS representing less than 10% body surface area (BSA); SJS/TEN overlap, 10% to 30% BSA; and TEN, greater than 30% BSA. In-hospital mortality in adults has been estimated to be between 12% and 40% based on the extent of epidermal detachment at presentation.^1,2 A recent study in the United States, based on diagnosis codes from the Nationwide Inpatient Sample, reported mortality rates of 4.8% for SJS, 19.4% for SJS/TEN overlap, and 14.8% for TEN.³ Unfortunately, the rarity of the disease makes it difficult to collect generalizable information to understand patient prognosis.