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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?

Learning Objectives

  1. What are common toxicities of immunotherapy?

  2. How are the toxicities graded?

  3. How are lower and higher grade toxicities of immunotherapy treated?

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

The development of this novel class of immune-based therapy presents new challenges in recognizing and managing a spectrum of treatment-related toxicities.

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

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).

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.


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).

TABLE 21-1Grading Severity Scale for Adverse Events

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