Abstract
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.
Highlights
Cancer immunotherapy has revolutionized the treatment of cancer [1, 2]
In a landmark regulatory step, the Food and Drug Administration (FDA) recently approved both pembrolizumab and nivolumab for use in certain patients with mismatch repair deficient and microsatellite instability high (MSI-H) cancers that have progressed following treatment with chemotherapy – the first such ‘tissue-agnostic,’ biomarkerdriven approvals granted [5, 6]. Both anti-programmed death 1 (PD-1) agents are associated with negligible antibody-dependent cellmediated cytotoxicity (ADCC), a process that could be detrimental to the activation of T effector cells
Since May 2016, atezolizumab and durvalumab have both been approved for the treatment of non-small cell lung carcinoma (NSCLC) and urothelial carcinoma, and avelumab was approved for use in Merkel cell carcinoma and urothelial carcinoma [7,8,9]
Summary
Cancer immunotherapy has revolutionized the treatment of cancer [1, 2]. Currently, the most widely used approach is the administration of targeted monoclonal antibodies (mAbs) directed against regulatory immune checkpoint molecules that inhibit T cell activation [1]. In a landmark regulatory step, the FDA recently approved both pembrolizumab and nivolumab for use in certain patients with mismatch repair deficient (dMMR) and microsatellite instability high (MSI-H) cancers that have progressed following treatment with chemotherapy – the first such ‘tissue-agnostic,’ biomarkerdriven approvals granted [5, 6] Both anti-PD-1 agents are associated with negligible antibody-dependent cellmediated cytotoxicity (ADCC), a process that could be detrimental to the activation of T effector cells. Since drug labels for FDA-approved checkpoint inhibitors are based on clinical trial data for individual drugs and do not always align across therapeutic class, clinicians need multidisciplinary, broad perspective guidance on how to manage organ-specific toxicities To this end, the Society for Immunotherapy of Cancer (SITC) established a Toxicity Management Working Group to develop consensus recommendations on management of irAEs that develop following ICI therapy until evidencebased data are available to inform clinical decision-making. The results represent consensus thinking by a multidisciplinary group of experts in the field but should not replace sound clinical judgment or personalized drug management, as immunotherapy patients often require highly individualized management
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