Leading oncologists shared their experiences and insights on managing adverse events (AEs) in patients receiving dual checkpoint inhibition plus chemotherapy for non-small cell lung cancer (NSCLC), highlighting both challenges and practical approaches to treatment.
Dr. Patrick Forde, Director of the Thoracic Cancer Clinical Research Program at Johns Hopkins Medicine, led the discussion on safety considerations for combination immunotherapy regimens, particularly focusing on the CheckMate 9LA trial protocol.
Safety Profile and Treatment Selection
The combination of ipilimumab and nivolumab with chemotherapy presents distinct toxicity patterns compared to single-agent immunotherapy. Common treatment-related adverse events include skin reactions, endocrine abnormalities, and gastrointestinal issues, with colitis being particularly notable with CTLA-4 inhibition.
"You'll see skin toxicity and endocrine toxicity. GI toxicity is going to be more common with a CTLA-4 inhibitor, so colitis, gastritis, those sorts of things," explained Dr. Forde. He noted that hepatic and renal complications occur more frequently than with pembrolizumab-based regimens.
Managing Severe Adverse Events
When severe immune-related adverse events occur, experts emphasize the importance of prompt intervention. For grade 3 diarrhea, the consensus approach includes:
- Immediate treatment interruption
- Ruling out infectious causes
- Initiating high-dose corticosteroids (1 mg/kg/day)
- Obtaining gastroenterology consultation when available
- Considering CT imaging to confirm colitis
Dr. Melhem Jabbour emphasized the importance of ruling out Clostridioides difficile infection before starting immunosuppression: "You need to be sure they don't have colitis from immunotherapy because this can be miserable. I will stop [therapy] and scan, and sometimes get a gastroenterologist on board."
Special Patient Populations
The experts highlighted specific considerations for certain patient subgroups. Dr. Mohamad Khasawneh noted that dual checkpoint inhibition might be particularly beneficial for patients with poor prognostic factors: "I offer the anti–CTLA-4/PD-1 combination, especially in patients with low PD-L1 and central nervous system metastasis because that confers a worse prognosis."
Challenges in Rural Settings
Healthcare providers in rural areas face additional challenges in managing immune-related adverse events. Limited access to specialists often requires oncologists to manage complications independently. Dr. Jabbour shared his experience: "We [serve] a rural area where it's sometimes not easy to get everybody on board, and we have to manage [irAEs] ourselves most of the time."
Treatment Rechallenge Considerations
The decision to rechallenge patients with immunotherapy after severe adverse events requires careful consideration. Dr. Forde advised against rechallenge in cases of life-threatening toxicities such as myocarditis or myasthenia gravis. However, for certain patients who experienced good initial responses and developed toxicities requiring infliximab, rechallenge might be considered after careful evaluation.
Emerging Challenges
Dr. Stanley Nabrinsky raised concerns about the attribution of neurological complications to immunotherapy: "Neurological complications of immune oncology are an undiscovered territory." This highlights the need for better understanding and guidance regarding neurological adverse events in immunotherapy patients.
The experts emphasized that successful management of immune-related adverse events often requires a balanced approach between maintaining effective cancer treatment and managing toxicities. The increasing use of these therapies in earlier-stage disease further underscores the importance of vigilant monitoring and prompt intervention when complications arise.
