Julie R. Brahmer, MD
John A. Thompson, MD
As reported in the Journal of Clinical Oncology by Julie R. Brahmer, MD, of Johns Hopkins Kimmel Cancer Center, and colleagues, ASCO has released a clinical practice guideline on management of immune-related adverse events in patients receiving immune checkpoint inhibitor therapy.1 Immune checkpoint inhibitors include the anti-cytotoxic T-lymphocyte–associated protein 4 antibody ipilimumab (Yervoy), the anti–programmed cell death protein 1 antibodies nivolumab (Opdivo) and pertuzumab (Perjeta), and the anti–programmed cell death ligand 1 antibodies durvalumab (Imfinzi), atezolizumab (Tecentriq), and avelumab (Bavencio). To develop the guideline, ASCO brought together a multidisciplinary, multiorganizational panel of experts in medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, hematology, emergency medicine, nursing, clinical trials, and advocacy. The expert panel was co-chaired by Dr. Brahmer and John A. Thompson, MD, of the Seattle Cancer Care Alliance, University of Washington, and Fred Hutchinson Cancer Research Center.
The need for the guideline is summarized by the authors as follows: “Despite the often durable clinical benefits of the immune checkpoint blockade therapy, immune checkpoint inhibitor use is associated with a spectrum of adverse effects related to the mechanism of action that is quite different from other systemic therapies such as cytotoxic chemotherapy. The adverse effects can affect multiple organs of the body and are most commonly seen in the skin, gastrointestinal tract, and lungs, and in the endocrine, thyroid, adrenal, pituitary, musculoskeletal, renal, nervous, hematologic, cardiovascular, and ocular systems, and there should be a high level of suspicion that any changes are treatment-related…. Immune checkpoint inhibitor therapy can usually continue in the presence of mild [immune-related adverse events] with close monitoring. However, moderate to severe immune-related adverse events may be associated with severe declines in organ function and quality of life, and fatal outcomes have been reported; hence, these toxicities require early detection and proper management.”
Patient and family caregivers should receive timely and up-to-date education about immunotherapies, their mechanism of action, and the clinical profile of possible immune-related adverse events prior to initiating therapy and throughout treatment and survivorship.— Julie R. Brahmer, MD; John A. Thompson, MD; and colleagues
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The expert panel conducted a systematic review of publications on immune checkpoint inhibitor therapy from 2000 through 2017 and identified 204 relevant publications, with much of the evidence consisting of systematic reviews of observational data, consensus guidelines, case series, and case reports. As stated by the authors, due to the paucity of high-quality evidence on management of immune-related adverse events, recommendations are based on expert consensus.
The following summarizes/reproduces general recommendations to be followed irrespective of affected organs. The guideline provides detailed recommendations for organ-specific management for skin, gastrointestinal, lung, endocrine, musculoskeletal, renal, nervous system, hematologic, cardiovascular, and ocular immune-related adverse events. All recommendations in the guideline are based on expert consensus, with the assessment that benefits outweigh harms, and moderate strength of recommendation.
Patient and family caregivers should receive timely and up-to-date education about immunotherapies, their mechanism of action, and the clinical profile of possible immune-related adverse events prior to initiating therapy and throughout treatment and survivorship.
There should be a high level of suspicion that new symptoms are treatment-related.
In general, immune checkpoint inhibitor therapy should be continued with close monitoring for grade 1 toxicities, with the exception of some neurologic, hematologic, and cardiac toxicities.
Immune checkpoint inhibitors should be held for most grade 2 toxicities and resumption considered when symptoms and/or laboratory values revert to grade 1 or less. Corticosteroids (initial dose of 0.5 to 1 mg/kg/d of prednisone or equivalent) may be administered.
Immune checkpoint inhibitors should be held for grade 3 toxicities and high-dose corticosteroids (prednisone at 1–2 mg/kg/d or methylprednisolone intravenously at 1–2 mg/kg/d) initiated. Corticosteroids should be tapered over the course of at least 4 to 6 weeks. If symptoms do not improve with 48 to 72 hours of high-dose corticosteroid, infliximab (Remicade) may be offered for some toxicities.
When symptoms and/or laboratory values revert to grade 1 or less, re-challenge with immune checkpoint inhibitor may be offered; however, caution is advised, especially in those patients with early-onset immune-related adverse events. Dose adjustments are not recommended.
In general, grade 4 toxicities warrant permanent discontinuation of immune checkpoint inhibitors, with the exception of endocrinopathies that have been controlled by hormone replacement.
Additional information is available at www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki. ■
DISCLOSURE: For full disclosures of the study authors, visit www.ascopubs.org.
1. Brahmer JR, Lacchetti C, Schneider BJ, et al: Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. February 14, 2018 (early release online).
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