ASCO has released new recommendations for the management of adverse events related to two immunotherapy modalities with increasing application in cancer care—immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cell therapy. The recommendations were published as two separate guidelines and based on the findings from relevant literature published between 2017 and 2021.1,2
Managing Immune-Mediated Side Effects of Immune Checkpoint Inhibitor Therapy
“The purpose of the updated [immune checkpoint inhibitor] guideline is to help guide providers who treat patients with [immune checkpoint inhibitors] in the management of side effects from these agents,” said Bryan J. Schneider, MD, of the University of Michigan and Co-Chair on the guideline. “In addition, this update aims to provide new options for the management of steroid-refractory side effects.”
Bryan J. Schneider, MD
Dr. Schneider explained that immune checkpoint inhibitor–related side effects are very different from what oncologists are used to seeing with chemotherapy, where neutropenia, hair loss, and nausea are commonly observed. Immune-mediated side effects associated with immune checkpoint inhibitor treatment more often involve the skin (rashes), the endocrine (hypothyroidism), and gastrointestinal organs or systems (diarrhea and colitis).
“With the exception of some of the endocrine toxicities, most of these side effects are initially managed with steroids,” he said, noting that most providers are comfortable prescribing steroids, which are typically highly effective. “The problem is when the steroids are not controlling the side effects. Oftentimes, there’s a discomfort about what to do next.” Another challenge, he added, is that these toxicities almost uniformly blindside the treating clinician.
The latest recommendations aim to relieve some of the challenges faced in the clinic and account for different clinical scenarios after immune checkpoint inhibitor treatment by providing detailed recommendations on how to evaluate and manage immune checkpoint inhibitor–related side effects. The guideline covers the management of inflammatory dermatitis, bullous dermatoses, severe cutaneous adverse reactions, colitis, hepatitis, and pneumonitis, as well as endocrine, renal, nervous system, musculoskeletal, cardiovascular, ocular, and systemic toxicities. It also provides detailed information on the indications and contraindications for the use of immunosuppressive agents, while a special section is dedicated to the prevention and management of adverse events related to steroid use.
Managing the Adverse Effects of CAR T-Cell Therapy
Similarly, the purpose of the CAR T-cell guideline is “to offer some expert guidance and recommendations on the management of immune-related adverse events in patients who receive CAR T-cell therapy,” said Monalisa Ghosh, MD, of the University of Michigan Rogel Cancer Center, and CAR T-cell guideline panelist.
Monalisa Ghosh, MD
The guideline provides recommendations on the diagnosis, evaluation, and management of the most common toxicities of CAR T-cell therapy, including cytokine-release syndrome and immune effector cell–associated neurologic syndrome (ICANS). It also addresses less common toxicities, such as B-cell aplasia, prolonged and recurrent cytopenias, coagulopathies, infection, and hemophagocytic lymphohistiocytosis.
Dr. Ghosh explained that cytokine-release syndrome is the most common toxicity that occurs after a CAR T-cell infusion. “It’s a syndrome that’s characterized by immune activation and inflammation, so patients typically present with symptoms that are often similar to infection, such as fever, low blood pressure, low oxygen levels, high heart rate, shortness of breath, rash, headaches, and nausea,” she said. “What we are recommending for [cytokine-release syndrome] is the use of a few different therapies [based on severity]. For lower grade [cytokine-release syndrome], we recommend using anti–IL-6 therapies, such as tocilizumab; for higher grade [cytokine-release syndrome], steroids.”
“For ICANS, the mainstay of therapy is really steroids because the anti–IL-6 therapy that is given systemically has not been shown to be effective,” she added. “In cases that are refractory to steroid therapy, we really do not have any proven therapies that work very well.”
Furthermore, the guideline expert panel recommended that steroids be rapidly tapered once symptoms improve to grade 1. Short-term toxicities associated with CAR T-cell therapy should first be managed with supportive care, followed by pharmacologic interventions in patients whosecondition does not improve.
Improving Cancer Care in Regional Oncology Clinics
Both panelists are hopeful that these latest recommendations will provide clear guidance in an area of oncology practice that has been difficult for clinicians to navigate outside of tertiary and quaternary care centers.
“A lot of providers in oncology may not have that type of expertise readily accessible,” Dr. Schneider said. He emphasized that it is often impossible to refer every patient to a tertiary care center given the sheer number of patients that are now receiving, or are eligible, for some form of immune checkpoint inhibitor therapy. According to the estimates from 2018, this amounts to approximately 44% of all patients with cancer, the majority of whom will likely be managed in regional oncology clinics or hospitals.3
“We hope that the guidelines will become a quick reference tool for providers if they suspect one of these toxicities. Each toxicity section provides guidance on the typical symptoms, appropriate grading, workup, and treatment options,” he said.
“I believe that [these guidelines] will be helpful for more local and regional areas,” Dr. Ghosh said. “Right now, CAR T-cell therapy is mainly done at larger tertiary care centers; however, things are changing, and various regional facilities are starting to do CAR T-cell therapy. And even if they don’t do CAR T-cell therapy, a lot of the physicians will see these patients locally after they have developed toxicities from CAR T-cell infusions they received elsewhere.”
She also noted that she expects the major impact of these guidelines to be in streamlining the process of managing immunotherapy-related toxicities, because, at present, there is a lot of variability in the approaches between different centers. “Right now, these guidelines give us a chance to be consistent in what we do in the field across the various centers,” Dr. Ghosh said.
REFERENCES
3. Haslam A, Prasad V: Estimation of the percentage of US patients with cancer who are eligible for and respond to checkpoint inhibitor immunotherapy drugs. JAMA Netw Open 2:e192535, 2019.
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, November 3, 2021. All rights reserved.
