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Measuring Response to Immunotherapy in Melanoma

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Now that several immunotherapies are available for the treatment of malignant melanoma, questions remain concerning how to measure response and when to continue or discontinue therapy. Ascertaining true progression from pseudoprogression, an inflammatory immunologic response in which the melanoma looks like it is progressing when it is actually responding, can result in a great deal of angst, notes Anna Pavlick, DO.

When assessing a patient for response to a checkpoint inhibitor, their symptoms and condition are the most important factor, with imaging results and laboratory values as a secondary measure. When the patient is the same or better and the scan looks worse, Pavlick typically watches for another 6 to 8 weeks to determine what’s really happening. If the patient is taking an anti-PD-1 inhibitor, scans should be repeated in 12 weeks, unless something deteriorates clinically, Richard Joseph, MD, adds.

It’s not uncommon for new lesions to form or current lesions to get larger before a response is seen to immunotherapy, explains Robert Andtbacka, MD. For instance, in the phase III OPTiM study that examined talimogene laherparepvec (T-VEC), an intralesionally administered oncolytic virus, almost half of patients who ultimately achieved a durable response had growth of their initial melanoma beforehand. It’s important to recognize that responses are delayed with immunotherapy, Andtbacka notes.

In the OPTiM study, durable responses, the primary endpoint of the study, were seen in 16% of patients treated with T-VEC compared with 2% with the comparator, GM-CSF. In the final analysis for overall survival, a 4.4-month extension was noted; however, this was not deemed statistically significant (P = .051).

Delayed responses or pseudoprogression prior to achieving a response was first identified with the CTLA-4 inhibitor ipilimumab, notes Howard Kaufman, MD. This phenomenon occurs less frequently with PD-1 inhibitors or interleukin-2. If a response is seen but there are persistent lesions, a PET scan can be utilized to verify the response, Kaufman advises. An isolated persistent lesion can be treated locally with surgery or radiotherapy.

Therapy should be continued in patients with stable disease on immunotherapy, since these patients experience an overall survival similar to those who achieve a classic complete remission, Omid Hamid, MD, suggests. Achieving stable disease is more meaningful with immunotherapy, which is important as research into checkpoint inhibition moves outside of melanoma.

Patients with prolonged stable disease who want to discontinue therapy should be monitored with CT or PET scans every 3 months, Andtbacka states. It’s not uncommon to conduct a surgery on a patient with stable disease and find that there is only fibrosis there and no active tumor. From that perspective, treating patients in a truly multidisciplinary setting is the most beneficial approach.

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Daniel Olson, MD
Vishal Patel, MD, FAAD, FACMS, associate professor, Dermatology, George Washington (GW) School of Medicine & Health Sciences
Omid Hamid, MD, professor, medicine, Cedars-Sinai; director, Clinical Research and Immunotherapy, director, Cutaneous Oncology and Melanoma, The Angeles Clinic and Research Institute