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OncLive® will be LIVE with OncLive® News Network: On Location at the 2023 ASCO Annual Meeting. Each day, we will broadcast a series of interviews with top thought leaders, to learn their thoughts and reactions to data presented across oncology during the conference.

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Looking at the Latest Data in Lung Cancer at ASCO 2023: Dr Naidoo 

Jarushka Naidoo, MBBCh, assistant professor of oncology, Johns Hopkins University, discusses considerations for managing immune-related adverse events (irAEs) in patients with non—small cell lung cancer (NSCLC).

Generally, the mechanisms of immunotherapy and how they work in a patient’s body are different from chemotherapy, and as such, the side effect profile is also different. It is important for physicians to have a conversation with patients about the irAEs before beginning treatment. Because immunotherapy stimulates the patient’s immune system, inflammation can occur in any part of the body, Naidoo says.

Common adverse events associated with chemotherapy are fatigue, nausea, and skin rash—these are also seen with immunotherapy. However, toxicities specific to immunotherapy include colitis, inflammation of the colon; pneumonitis, inflammation of the lung; and hepatitis, inflammation of the liver. There are also severe irAEs to be aware of, such as myocarditis, inflammation of the heart, and encephalitis, inflammation of the lining of the brain. It is important to tell patients that although these events are rare, they can occur.

Fortunately, most irAEs can be managed with steroids. Naidoo urges any physician who feels uncomfortable managing a certain irAE to contact another medical oncologist who may have more experience in that area for insight.

Jarushka Naidoo, MBBCh, assistant professor of oncology, Johns Hopkins University, discusses considerations for managing immune-related adverse events in patients with non–small cell lung cancer.

Dr. Naidoo on Considerations for Managing irAEs in NSCLC

Jarushka Naidoo, MBBCh, assistant professor of oncology, Johns Hopkins University, discusses the mechanisms behind immune-related adverse events (irAEs) in lung cancer.

The reasons why some people develop certain AEs are different based on what the AEs are, says Naidoo. Some irAEs may be related to the formation of antibodies or autoantibodies against certain cells. Toxicities within the thyroid gland may be due to thyroid antibodies. Hypophysitis can be due to the patient having antibodies against some of the cells of the pituitary gland, adds Naidoo.

Other toxicities may be mediated by other inflammatory markers known as cytokines. Patients who receive chimeric antigen receptor T-cell therapy, for example, may develop cytokine release syndrome that is mediated by interleukin-6 (IL-6). Giving an anti—IL-6 or tocilizumab (Actemra) can help those patients, says Naidoo.

Researchers are actively studying many of these AEs. Johns Hopkins University was the first group to describe patients experiencing inflammatory arthritis as an AE of checkpoint inhibitors. Additional investigation into blood samples may also help physicians understand why patients may have developed those AEs, concludes Naidoo.

Dr. Naidoo on the Mechanisms Behind Immune-Related Adverse Events in Lung Cancer

Jarushka Naidoo, MBBCh, assistant professor of oncology, Johns Hopkins University, discusses the treatment of patients with non—small cell lung cancer who develop immune-related adverse events (irAEs).

The overall incidence of irAEs is low, says Naidoo. The incidence is about 5% or less with single-agent immunotherapy drugs and around 10% for some combinations. However, the incidence of severe irAEs with the combination of ipilimumab (Yervoy) and nivolumab (Opdivo) can be upwards of 30%.

In many cases, irAEs are effectively treated with corticosteroid medications, says Naidoo. Eighty percent or higher of patients with pneumonitis are treated effectively with steroids, so that the pneumonitis improves or resolves. However, in a small percentage of these toxicities, steroids may not be sufficient.

In patients who have colitis that does not improve after 48 hours, physicians tend to offer them a second immunosuppressive agent. For colitis, physicians give infliximab (Remicade). Depending on what the toxicities are, those second immunosuppressive agents may be different, explains Naidoo. For hepatitis, physicians give mycophenolate mofetil, but for certain toxicities, such as pneumonitis, the optimal second agent is not actually known. This is actively being studied, states Naidoo.

Jarushka Naidoo, MBBCh, assistant professor of oncology, Johns Hopkins University, discusses the treatment of patients with non–small cell lung cancer who develop immune-related adverse events (irAEs).

Dr. Naidoo on Treating Immune-Related Adverse Events in NSCLC

Jarushka Naidoo, MBBCh, assistant professor of oncology, Johns Hopkins University, discusses managing immune-related adverse events (irAEs) in patients with non—small cell lung cancer (NSCLC).

 can be varied, so any change in the clinical condition of the patient that is different from when they began the immunotherapy should trigger a warning sign for physicians, explains Naidoo. The overall incidence of irAEs events is low—approximately 5% or less with single-agent immunotherapy and approximately 10% with some combinations. The incidence of severe side effects can be up to 30% with the combination of ipilimumab (Yervoy) and nivolumab (Opdivo), notes Naidoo.

The side effects that physicians are the most concerned about are colitis resulting from ipilimumab, which tends to cause diarrhea and pain in the abdomen. Additional cause for concern is pneumonitis from anti—PD-1 agents, and shortness of breath or cough that is new. Additionally, new or increased fatigue can result from the immunotherapy itself, or what can lead to a diagnosis of an endocrinopathy like thyroid dysfunction, pituitary dysfunction, or diabetes, states Naidoo.

Jarushka Naidoo, MBBCh, assistant professor of oncology, Johns Hopkins University, discusses managing immune-related adverse events (irAEs) in patients with non–small cell lung cancer (NSCLC).

Dr. Naidoo on Managing Immune-Related Adverse Events in NSCLC

Jarushka Naidoo, MBBCh, assistant professor of oncology, Johns Hopkins University, discusses studies investigating immune-related adverse events for patients with lung cancer.

In the pneumonitis field, there was a study published in the 

 in 2017 of a collaboration between Memorial Sloan Kettering Cancer Center and the Melanoma Institute of Australia. That series included more than 40 patients with solid tumors who developed pneumonitis as a result of immune checkpoint inhibitors. These were mainly patients with lung cancer and melanoma. What was novel about that study was that it comprehensively reported that pneumonitis can occur at any time during the treatment of a patient with immunotherapy. It has since been reported that this can even occur after immunotherapy has stopped, explains Naidoo.

The other seminal observation, which is highlighted in the guidelines, is that each case of pneumonitis is not all created equal, says Naidoo. There may be variable radiographic appearances associated with it. Clinicians should be aware that if a patient develops a new cough, shortness of breath, fever, or chest pain, and they do a CT scan, that pneumonitis doesn't have a classic appearance. The appearances may range from organizing pneumonia, ground glass opacities, hypersensitivity, interstitial, or not otherwise specified, which is a mix of all 4 of those appearances.

Dr. Naidoo on Studies of Immune-Related Adverse Events in Lung Cancer

Jarushka Naidoo, MBBCh, assistant professor of oncology, Johns Hopkins University, discusses advancements in the management of immune-related adverse events (irAEs) in patients with lung cancer during the 5th Annual Miami Lung Cancer Conference.

In the past few years, there have been several guidelines published to assist physicians with diagnosing and identifying immune-related side effects. Pneumonitis is the most common irAE seen in patients with lung cancer, Naidoo says, and it can be difficult to discern the difference between pneumonitis and pneumonia or progression of lung cancer.

It is widely accepted practice now that patients receive a high-resolution CT scan, but they can have a chest xray to start. Patients who are symptomatic should be considered for a bronchoscopy with or without a lung biopsy in order to tell if a patient has pneumonitis.

Jarushka Naidoo, MBBCh

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