Immune effector cell (IEC) therapies offer durable and sustained remissions in significant numbers of patients with hematological cancers. While these unique immunotherapies have improved outcomes for pediatric and adult patients in a number of disease states, as ‘living drugs,’ their toxicity profiles, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), differ markedly from conventional cancer therapeutics. At the time of article preparation, the US Food and Drug Administration (FDA) has approved tisagenlecleucel, axicabtagene ciloleucel, and brexucabtagene autoleucel, all of which are IEC therapies based on genetically modified T cells engineered to express chimeric antigen receptors (CARs), and additional products are expected to reach marketing authorization soon and to enter clinical development in due course. As IEC therapies, especially CAR T cell therapies, enter more widespread clinical use, there is a need for clear, cohesive recommendations on toxicity management, motivating the Society for Immunotherapy of Cancer (SITC) to convene an expert panel to develop a clinical practice guideline. The panel discussed the recognition and management of common toxicities in the context of IEC treatment, including baseline laboratory parameters for monitoring, timing to onset, and pharmacological interventions, ultimately forming evidence- and consensus-based recommendations to assist medical professionals in decision-making and to improve outcomes for patients.

Inflammatory diseases include a wide variety of highly prevalent conditions with high mortality rates in severe cases ranging from cardiovascular disease, to rheumatoid arthritis, to chronic obstructive pulmonary disease, to graft vs. host disease, to a number of gastrointestinal disorders. Many diseases that are not considered inflammatory per se are associated with varying levels of inflammation. Imaging of the immune system and inflammatory response is of interest as it can give insight into disease progression and severity. Clinical imaging technologies such as computed tomography (CT) and magnetic resonance imaging (MRI) are traditionally limited to the visualization of anatomical information; then, the presence or absence of an inflammatory state must be inferred from the structural abnormalities. Improvement in available contrast agents has made it possible to obtain functional information as well as anatomical. In vivo imaging of inflammation ultimately facilitates an improved accuracy of diagnostics and monitoring of patients to allow for better patient care. Highly specific molecular imaging of inflammatory biomarkers allows for earlier diagnosis to prevent irreversible damage. Advancements in imaging instruments, targeted tracers, and contrast agents represent a rapidly growing area of preclinical research with the hopes of quick translation to the clinic.

Brentuximab vendotin is a monoclonal antibody approved in August 2011 for use in patients with Hodgkin disease and a rare systemic lymphoma known as anaplastic large cell lymphoma. Brentuximab is approved in patients with Hodgkin disease who have failed autologous transplantation or after failure of at least two prior multi-agent chemotherapy regimens but has not been studied following allogeneic transplantation. Four patients with relapsed Hodgkin disease have been treated at our institution with at least two doses of brentuximab vendotin. Two patients have experienced significant infusion reactions on multiple occasions, and two patients have tolerated the infusions well. During phase 2 trials, there were no reports of Grade 3 or 4 infusion-related reactions. Both patients with reactions had relapsed following allogeneic stem cell transplants, while neither of the patients who tolerated the infusions had undergone transplantation. We report our experience with brentuximab vendotin-treated patients at our institution, focusing on the two post-allogeneic patients who experienced multiple significant infusion reactions. This report evaluates possible mechanisms behind their reactions, including previous allogeneic stem cell transplantation as a likely precipitating factor.