Cancer immunotherapy has transformed the treatment of cancer. However, increasing use of immune-based therapies, including the widely used class of agents known as immune checkpoint inhibitors, has exposed a discrete group of immune-related adverse events (irAEs). Many of these are driven by the same immunologic mechanisms responsible for the drugs’ therapeutic effects, namely blockade of inhibitory mechanisms that suppress the immune system and protect body tissues from an unconstrained acute or chronic immune response. Skin, gut, endocrine, lung and musculoskeletal irAEs are relatively common, whereas cardiovascular, hematologic, renal, neurologic and ophthalmologic irAEs occur much less frequently. The majority of irAEs are mild to moderate in severity; however, serious and occasionally life-threatening irAEs are reported in the literature, and treatment-related deaths occur in up to 2% of patients, varying by ICI. Immunotherapy-related irAEs typically have a delayed onset and prolonged duration compared to adverse events from chemotherapy, and effective management depends on early recognition and prompt intervention with immune suppression and/or immunomodulatory strategies. There is an urgent need for multidisciplinary guidance reflecting broad-based perspectives on how to recognize, report and manage organ-specific toxicities until evidence-based data are available to inform clinical decision-making. The Society for Immunotherapy of Cancer (SITC) established a multidisciplinary Toxicity Management Working Group, which met for a full-day workshop to develop recommendations to standardize management of irAEs. Here we present their consensus recommendations on managing toxicities associated with immune checkpoint inhibitor therapy.Electronic supplementary materialThe online version of this article (10.1186/s40425-017-0300-z) contains supplementary material, which is available to authorized users.

Pulmonary infiltrates frequently complicate hematopoietic SCT (HSCT). The utility of fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage (BAL) in the evaluation of new pulmonary infiltrates, particularly as it relates to optimal timing of the procedure, is unclear. Based on this, we retrospectively reviewed 501 consecutive, adult, nonintubated patients who underwent 598 BALs for evaluation of new pulmonary infiltrates during the first 100 days following HSCT to determine whether diagnostic yields for infection, subsequent antimicrobial treatment modifications and patient outcomes differed following early vs late referrals for the procedure. The overall yield of BAL for clinically significant pathogens was 55%. Notably, the yield was 2.5-fold higher among FOBs performed within the first 4 days of presentation (early FOB) compared to those performed late, and highest (75%) when performed within 24 h of clinical presentation. Rates of FOB-guided adjustments in antimicrobial therapy (51%) did not differ significantly between early and late examinations. However, late FOB-related antibiotic adjustments were associated with 30-day pulmonary-associated deaths that were threefold higher (6 vs 18%, P ¼ 0.0351). Major FOB-related complications occurred in only three (0.6%) patients. We conclude that early referral for FOB in this patient setting is associated with higher diagnostic yields and may favorably impact survival.

Although hematopoietic stem cell transplantation (HSCT) can be curative in patients with certain malignancies, survival is poor if the recipient becomes critically ill. This prospective study examined the outcomes of 115 consecutive HSCT patients admitted to the medical intensive care unit (MICU) of a tertiary cancer center and identified variables associated with survival. The need for endotracheal intubation and mechanical ventilation ("intubation") had a profound adverse effect on survival. Overall, 9 of 48 (18.8%) intubated patients survived compared with a survival rate of 44 of 67 (65.7%) among patients not intubated (p < 0.001). This pattern persisted for nearly all patient subgroups. Among intubated patients, those receiving peripheral blood stem cell transplant (PBSCT) had significantly better survival than bone marrow transplant (BMT) patients (8 of 26, 31% versus 1 of 22, 4%; p = 0.028). Multiple logistic regression analyses indicated that the probability a patient admitted to the MICU survived decreased significantly if the patient was intubated, had an allogeneic rather than autologous transplant, had an infection or gastrointestinal bleeding, and also decreased with higher respiratory rate, higher heart rate, longer time from transplant to MICU admission or higher bilirubin. These results may be of value in deciding which critically ill patients will benefit from intubation following major complications after HSCT transplantation.

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