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Melanoma Think Tank

CME

Think Tank on Melanoma: Optimizing Therapy for Patients in an Evolving Treatment Landscape

Physicians: Maximum of 1.00 AMA PRA Category 1 Credit™

Released: August 02, 2023

Expiration: August 01, 2024

Evan J. Lipson
Evan J. Lipson, MD
CME/CE Information

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Spectrum of Immune-Related Toxicity

Immune checkpoint inhibitors are associated with a spectrum of toxicities that can include any organ system.39 These toxicities differ from those associated with chemotherapy and targeted agents. The diagram shows some examples of how immune-related toxicities might manifest.

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General Management of irAEs Associated With Immune Checkpoint Inhibitors

In general, we categorize toxicities as mild, moderate, or severe and classify them by grade.40-42 For most cases of grade 1 toxicities, we administer supportive therapy and can continue immune checkpoint inhibitors.  

For patients with grade 2 irAEs, corticosteroid initiation might be required, and for selected irAEs we hold the immune checkpoint inhibitor therapy.
  
In cases of grade 3 or 4 irAEs, we generally withhold or discontinue immune checkpoint inhibitor therapy and add systemic corticosteroids. Any time we use systemic corticosteroids, they should be tapered over ≥4 weeks. In some cases, if toxicities are steroid refractory, administration of alternative immunosuppressive therapies such as infliximab may be required.  

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NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Managing Immune Checkpoint Inhibitor–Related Toxicities

Several guidelines for the management of irAEs are available, including those from the National Comprehensive Cancer Network. Clinical Care Options has an interactive tool based on these guidelines that allows you to enter the specific organ system affected and the severity of the irAE and see guideline-based recommendations for management.

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Adverse Events Associated With Combination BRAF/MEK-targeted Therapy

The toxicity profiles of the 3 FDA-approved BRAF/MEK inhibitor combinations are slightly different from one another.43-45

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BRAF/MEK Inhibitor Combination Adverse Event Management

When we initiate therapy with BRAF/MEK inhibitors, we discuss possible dermatologic AEs such as rash and the development of other skin cancers.46,47

We also perform baseline retinal evaluations. Any patient with complaints of visual disturbance needs a rapid ophthalmology evaluation and withholding of BRAF/MEK inhibitor therapy, which is often temporary.

For all patients starting on BRAF/MEK inhibition, we obtain a baseline echocardiogram and then repeat those tests monthly for 3 months, then every 3 months.

Serum hepatic transaminases sometimes increase in patients on BRAF/MEK inhibitor therapy combinations, so we monitor that monthly.

Pyrexia is a major AE, and its management can be challenging. Medication based fevers often require holding BRAF/MEK inhibitors and administering antipyretics and/or corticosteroids. Published guidelines provide pyrexia management for patients on these therapies.48

Diarrhea, nausea, and vomiting can be managed with supportive care as well as antidiarrheals and antiemetics.

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For a patient receiving nivolumab plus ipilimumab for stage IV melanoma who develops grade 2 diarrhea, in addition to close monitoring, which of the following proactive strategies would you use to manage this adverse event and decrease the possibility of worsening?

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