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This case involves a 68-year-old man diagnosed with metastatic non–small cell lung cancer (NSCLC) and adenocarcinoma histology with a programmed death ligand 1 (PDL-1) score of 35%. He completed 4 cycles of carboplatin, pemetrexed, and pembrolizumab combination treatment and is currently on pemetrexed and pembrolizumab maintenance treatment. He presented to the hospital with abdominal cramps, 6-8 episodes of bloody diarrhea in a day, and fatigue. An infectious etiology has been ruled out, and immune-related colitis is speculated. What treatment should be offered to this patient?
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Learning Objectives
What are common toxicities of immunotherapy?
How are the toxicities graded?
How are lower and higher grade toxicities of immunotherapy treated?
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In the past, limited success from traditional immunotherapy agents for most solid malignancies resulted in a perception that immunotherapy has only a limited role in oncology.1 However, with a better understanding of genetic patterns, predictive biomarkers such as PD-L1 and tumor mutational load have resulted in promising outcomes with immunotherapy.2-4
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The development of this novel class of immune-based therapy presents new challenges in recognizing and managing a spectrum of treatment-related toxicities.
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The toxicity profiles of these agents, including those that block immune checkpoints, immunostimulatory agents, and adoptive T-cell therapy, are the result of hyperactivated T cells and a surge of cytokines directed against normal tissue.5,6
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Immunotoxicity management is based on expert consensus, and a majority of the guidelines are obtained from the National Comprehensive Cancer Network (NCCN) with 2a category evidence (based on lower level evidence with a uniform consensus that intervention is appropriate).
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A detailed history and physical examination remain the key to approaching any new presenting complaints. Non-inflammatory (including infectious) etiology should be ruled out before considering drug toxicity. Hence, treatment-related toxicity should be a diagnosis of exclusion. An understanding of the timing, likelihood, and presentation of immune toxicity as well as how to manage the toxicity effectively will be a necessity for any health care provider dealing with cancer patients.
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Once the diagnosis of treatment-related toxicity is confirmed, management is based on a patient’s presenting grade. Common Terminology Criteria for Adverse Events v4.0 (CTCAE) provides a descriptive terminology that can be utilized for an adverse event (AE) and grading severity scale for each AE term (Table 21-1).
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