Immunotherapy in Melanoma

Immunotherapies have brought rapid and momentous advances—and at the same time, tricky management challenges, say clinicians from Boston Medical Center in Massachusetts. They report on a patient’s case that “underscores the complexity” of interpreting and managing the common and uncommon adverse effects of therapies.

Their patient, a 65-year-old man with metastatic melanoma, was started on ipilimumab and nivolumab. Two weeks after the first cycle, the patient came back to the hospital with symptoms of generalized fatigue and right upper quadrant abdominal pain; he was diagnosed with new ascites, leucocytosis, and normocytic anemia that required 2 transfusions. Magnetic resonance cholangiopancreatography showed a significant increase in tumor burden and mild left hepatic ductal dilation.

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Because of the worsening severity of the hepatic tumor load, the patient was switched to dabrafenib and trametinib. He improved clinically, and his liver function tests improved, but by day 5, the patient had developed disseminated intravascular coagulation and pancytopenia. Clinically, however, he seemed well, with stable haemodynamics and no signs of infection.

The patient was started on high-dose steroids, and continued on dabrafenib and trametinib. The next several days saw “dramatic improvement in all parameters,” according to his clinicians. The steroids were tapered, and the patient was discharged to a rehabilitation facility. The following week at an outpatient visit he had no symptoms or significant abnormalities in his laboratory values.

The clinicians note that their patient brings to life several of the management challenges of immunotherapies. Notably, in addition to the immune-related adverse events common to immunotherapies—including life-threatening effects—clinicians may be faced with pseudoprogression: an initial increase in the size of tumor lesions with subsequent improvement.

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Other challenges, the clinicians note, are deciding how to sequence new immunotherapies and when is the right time to treat with high-dose steroids. So far, they say, no studies have delineated the best sequence of treatment, particularly in combination with other targeted agents, such as BRAF inhibitors like dabrafenib.

The exciting new hope offered by the new therapeutic options, the clinicians conclude, is tempered by the need to resolve these and other questions. In the meantime, the unique management challenges require “vigilance and ongoing research.”

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Source:

Tran A, Sarosiek S, Ko NY. BMJ Case Rep. 2016; pii: bcr2016216681.
doi: 10.1136/bcr-2016-216681.