Immunotherapy Side Effects and OS in NSCLC

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NSCLC patients who developed immune-related adverse events during immunotherapy showed longer overall survival and progression-free survival than patients who did not.

A study of patients who received a form of immunotherapy for non–small cell lung cancer (NSCLC) found that patients may get more than one immune-related side effect, but that the presence of multisystem immune-related adverse events (irAEs) correlated with better response to treatment overall in terms of progression-free survival (PFS) and overall survival (OS).1

Cancer care is complicated, and the potential side effects that accompany it can have serious effects on a patient’s quality of life or even be fatal. For that reason, setting patients up with realistic expectations is key. Adverse events can also lead to nonadherence to medication regimens, which can cause further disease progression and even unnecessary hospitalizations, taxing both patients and the health care system.2

The study, which was published online in JAMA Oncology, aimed to identify the spectrum of irAEs that occur in NSCLC patients undergoing treatment with immune checkpoint inhibitors and find out whether patients with multisystem irAEs have improved survival after adjusting for treatment duration. Immune checkpoint inhibitors generally have fewer side effects than standard chemotherapy, but irAEs specifically can be difficult to manage in the patients who develop them.

The retrospective cohort study included 623 patients with stage III/IV NSCLC at 5 academic institutions worldwide who were treated with anti–PD-L1 immune checkpoint inhibitors either alone or in combination with another anticancer agent between January 2007 and January 2019. The cohort was 60% men and 77% White with a median age of 66 years.

Of the 623 patients involved, 148 (24%) developed single-organ irAEs, and 58 (9.3%) developed multisystem irAEs. In patients undergoing anti–PD-L1 monotherapy, the most common multisystem irAE patterns were pneumonitis thyroiditis (14%), hepatitis thyroiditis (10%), dermatitis pneumonitis (10%), and dermatitis thyroiditis (8%). Patients who were healthier overall based on Eastern Cooperative Oncology Group (ECOG) performance status were typically treated with PD-L1 inhibitors for longer but were at a greater risk of irAEs.

“While it makes sense that people who are fitter may be treated longer and have a higher risk of irAEs, this study accounted for treatment duration, and the association between irAEs and survival remains statistically robust,” study author Jarushka Naidoo, MBBCh, an adjunct professor at the Johns Hopkins Kimmel Cancer Center and a Bloomberg-Kimmel Institute for Cancer Immunotherapy investigator, said in a statement.3

Patients who had 1 irAE and multisystem irAEs were likely to live longer, with incrementally improved OS associated with the number of irAEs during treatment. OS was 8.7 months from diagnosis in patients with no irAEs, compared with 12.3 months in patients who developed 1 irAE and 21.8 months in patients who developed 2 irAEs . The median PFS in patients with no irAEs was 2.8 months, compared with 5.1 months and 10.9 months in patients with 1 or 2 irAEs, respectively.


“IrAEs are tricky because they are characteristically unpredictable,” Naidoo said. “They can develop within days—but also after many years of treatment, so patients and oncologists have to always be on the lookout for symptoms.” But given the association between irAEs and OS as well as PFS, immune checkpoint inhibitors are often the better option in patients with advanced cancer who respond to them, said Naidoo.

“We know that the outcome for most advanced cancers is poor, so the balance usually favors treatment with immune checkpoint inhibitors,” Naidoo said. “However, it is important for patients to be aware of immune side effects, that they may experience multiple immune side effects, and the implications on survival.”


1. Shankar B, Zhang J, Naqesh AR, et al. Multisystem immune-related adverse events associated with immune checkpoint inhibitors for treatment of non–small cell lung cancer. JAMA Oncol. 2020;6(12):1952-1956. doi:10.1001/jamaoncol.2020.5012

2. Harrison E. The Cost of Not taking our medicine: the complex causes and effects of low medication adherence. Am J Account Care. Published online November 29, 2018. Accessed December 17, 2020.

3. Drugs Create Balancing Act for Patients with Non-Small Cell Lung Cancer. News Release. Johns Hopkins Medicine; December 14, 2020. Accessed December 17, 2020.