COMMENTARY

Immunotherapy Complete Response Data Suggest Metastatic Melanoma Cures

Jeffrey S. Weber, MD, PhD

Disclosures

August 09, 2018

This is Dr Jeffrey Weber. I am a medical oncologist at the Laura and Isaac Perlmutter Cancer Center at New York University Langone Health in New York City.

Today we will be talking about a very interesting article that appeared several months ago in the Journal of Clinical Oncology,[1] which I think sheds light on whether or not immunotherapy can actually cure patients with melanoma. It was a study that has been described in part at a recent American Society of Clinical Oncology meeting, but now appears completely in print, with an awful lot of data that are very interesting. It describes patients who are complete responders in the original KEYNOTE-001 trial of pembrolizumab for patients who were either previously treated, or in one part [of the study] who had had no previous treatment, for their stage IV metastatic melanoma. In that trial, a total of 16%, or 105 patients, had a complete response (CR).

With a median follow-up of 43 months and more than 2 years on average since achieving a complete remission, 86% discontinued treatment, about 15 of them continued on treatment (with a median of over 40 months of therapy), and 63% stopped therapy for observation. The 2-year disease-free survival was 91%, which is very impressive. In those who were simply observed, it was 90%, which is a very impressive disease-free survival figure.

The authors looked at a variety of indicators—some of which are known prognostic factors for melanoma, and some of which I think were sort of interesting and original. They looked at lactate dehydrogenase (LDH) levels and found that the CR rate in those whose LDH was twice normal or more was very low; only one patient out of 105 had a CR. Most of the CRs, of course, were in those with normal LDH or those whose LDH was between 1 and 2 times the upper limit of normal. In fact, LDH as a prognostic factor for being a complete responder fell out when programmed death-ligand 1 (PD-L1) and tumor burden were taken into consideration. As we have heard before, tumor burden is a very important factor when considering the ability to have a good response and prolonged survival with a drug like pembrolizumab, which is a PD-1 blocking antibody.

Interestingly, the CR rate was increased in those who were BRAF wild-type. It was increased in those over 65 years, which is most unusual because it is in contradiction to what we often see with chemotherapy. As you might expect, those who had a performance status of 0 had a higher CR rate than those whose performance status was 1. Confirming data we have seen before, those who had lung-only disease or who had M1a or subcutaneous or dermal disease did much better in terms of CR than those who had liver disease. Liver disease only tends to be a pretty bad prognostic factor for those receiving PD-1 blockade. Disease burden is a very impressive indicator of the ability to achieve a CR and have prolonged survival, as we have seen for response in general with PD-1 blockade. Interestingly, as albumin levels decreased, they were associated with a worse outcome.

What is the conclusion of this paper? It says if you achieve a CR (which is not so infrequent, occurring in 16% of all patients in a very large trial of 655 patients), your chance of staying there at least at 2 years is very high. My personal prediction is that many of those in CR at 2 years who stay there will probably be cured of their melanoma. Again, in the immunotherapy era, we can now begin to talk of cures for patients with melanoma.

This is Dr Jeffery Weber. Please feel free to call in with comments, and I thank you for your attention.

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