The publication of the ASCO clinical practice guideline for the management of immune therapy–related adverse events—reviewed in this issue of The ASCO Post—represents an important next step in the incorporation of checkpoint blocking antibodies as standard cancer treatment modalities.1 The U.S. Food and Drug Administration (FDA)-approved antibodies leading to disinhibition of T cells by blocking cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) and the programmed cell death protein 1 (PD-1) pathways are now in standard widespread use across a subset of both solid tumor and hematologic malignancies. During clinical trials, it was recognized that these therapeutic agents mediated tissue-specific inflammation, resulting in toxicity to a wide variety of organs. This finding led to the development of algorithms for mechanism-based management, with careful monitoring and implementation of immune-suppressing medicines. These efforts resulted in a decrease in deaths to due toxicities such as enterocolitis.
Focus on Education and Safety
As checkpoint-blocking antibodies became available and entered standard use, the need for consistent guidelines for recommended management was apparent. Since these agents function via a mechanism that is distinct from most other anticancer agents, education about the timely detection of early signs of toxicity and consistent stepwise approaches to management were prioritized by many groups, including ASCO and the National Comprehensive Cancer Network® (NCCN®) for the current guideline.
Although therapeutic modalities may change, the fundamental role of guideline-based education to ensure patient safety remains as necessary as ever.— Jedd D. Wolchok, MD, PhD
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The team assembled to develop this guideline was composed of clinicians with deep experience from early clinical trials of checkpoint-blocking antibodies and experts in the efficient creation of clear guidance for cancer care. Together, we hope this guideline allows for the safer treatment of patients with immune-modulating agents. Continuing education is vital for our oncology workforce to quickly adapt to the rapid therapeutic advances resulting in new standard therapies.
Early in my experience, as a clinical investigator in the ipilimumab (Yervoy) program, I was sharing my experiences managing some of these new toxicities with my mentor, Dr. Alan Houghton. Alan reminded me that steep learning curves have always accompanied transformative therapies: “When we first started using cisplatin, we saw drug-related deaths. With more experience, we learned how to manage the side effects.” Although therapeutic modalities may change, the fundamental role of guideline-based education to ensure patient safety remains as necessary as ever.
Dr. Wolchok is a member of the ASCO expert panel that developed the clinical practice guideline and coauthor of the Journal of Clinical Oncology article reporting the guideline. ■
Dr. Wolchok is Chief, Melanoma & Immunotherapeutics Service, and Director, Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, New York.
DISCLOSURE: Dr. Wolchok has been a consultant/advisor to BMS, MedImmune, and Genentech.
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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