For patients with late-stage melanoma, however, checkpoint inhibitors can offer hope, once other treatment options have been exhausted. Approximately 30% to 40% of patients respond to treatment with a single checkpoint inhibitor, up from 20% several years ago. And that percentage can rise above 50% when patients receive 2 of these drugs.

“The numbers are pretty much all over the place,” conceded Joseph Markowitz, MD, PhD, a physician-scientist in the cutaneous oncology program at Moffitt Cancer Center in Tampa, Florida. “But, we do get some subsets of patients over 60% on dual agents.”

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Institutional preferences, he says, generally govern which checkpoint inhibitor doctors use first, though most prefer anti-PD1, he says, reserving the use of 2 drugs together for patients diagnosed with the heaviest burden of disease. But whether 2 checkpoint inhibitors work better than 1 and act synergistically, or if they are merely additive, he said, is not yet known.

As for IMPRES, Dr Markowitz described it “as a nice step forward scientifically.”

Perhaps, most importantly, he says, is that the study shows “there’s something about spontaneous regression and the mechanisms of anti-PD1 and anti-CTLA-4 that’s similar” — a connection awaiting further testing in larger cohorts and other cancers.

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Noam Auslander, PhD, from the Center for Cancer Research (CCR) at NCI, who is also the senior author of the study, says a clinical trial of IMPRES in patients with melanoma is the clear next step. Testing in other cancers, such as lung cancers, is further off, despite the promise immune checkpoint blockade may hold, she said. “Almost all the data we have right now come from melanoma.”


  1. Auslander N, Zhang G, Sang Lee J, et al. Robust predictor of response to immune checkpoint blockage therapy in metastatic melanoma [published online August 20, 2018]. Nature Med. doi: 10.1038/s41591-018-0157-9
  2. National Cancer Institute. NCI-led research team develops predictor for immunotherapy response in melanoma. NCI press release. Updated August 20, 2018. Accessed August 20, 2018.
  3. The American Society of Clinical Oncology and the National Comprehensive Cancer Network. Guidelines Planned on Management of Immunotherapy Side Effects. Updated February 16, 2017. Accessed September 12, 2018.