Memorial Sloan Kettering Team Makes Key Discovery in Understanding Immunotherapy’s Successes—And Its Failures

The gist: Some melanoma patients benefit from treatment with the drug ipilimumab (Yervoy), but others don’t. New research has found that people who benefit from ipilimumab tend to have certain genetic mutations in their tumor cells. This research could be used to develop a diagnostic test that could help doctors predict whether ipilimumab will work or not for a particular patient.

“A collaborative team of leaders in the field of cancer immunology from Memorial Sloan Kettering Cancer Center has made a key discovery that advances the understanding of why some patients respond to ipilimumab, an immunotherapy drug, while others do not.  MSK was at the forefront of the clinical research that brought this CTLA-4 blocking antibody to melanoma patients.

“A report published online first today in the New England Journal of Medicine shows that in patients who respond to ipilimumab, their cancer cells carry a high number of gene mutations—some of which make tumors more visible to the immune system, and therefore easier to fight.  The research was led by Vice Chair of Radiation Oncology and cancer genomics researcher Timothy Chan, MD, PhD ; oncology fellow Alexandra Snyder Charen, MD; and Chief of the Melanoma and Immunotherapeutics Service and the Lloyd J. Old Chair for Clinical Investigation Jedd Wolchok, MD, PhD.

“ ‘We are learning that there are few treatments that don’t have some footprint in the cancer genome,’ says Dr. Chan. ‘For the first time, it might be feasible to develop a reliable diagnostic test to help guide treatment decisions by predicting who will respond…’

“Eventually, these findings could translate into a diagnostic test to detect the mutations in melanoma patients. Results could help doctors and patients make more-informed treatment choices. In addition, the MSK team plans to investigate whether specific tumor mutations influence the effectiveness of other immunotherapy drugs. Dr. Chan says, ‘If we know a patient won’t respond to ipilimumab, we may be able to identify other drugs that are more likely to be effective against this person’s tumor.’ ”

Super Patient: Chelsea Price Takes Charge of Stage III Melanoma

Late in 2010, Chelsea Price’s boyfriend noticed that a mole on her upper back was scabbed and weeping. “It had always been there but he thought I should get it checked,” recalls Chelsea, who was then 23 years old. By the time her dermatology appointment rolled around, however, the mole had healed. “I almost cancelled,” she says.

Good thing she didn’t. At her follow-up appointment, her dermatologist casually said, “Hey, it’s melanoma.” Thinking he was kidding, Chelsea started laughing. When she realized he was serious, she was stunned. Continue reading…

Immunotherapies Take Center Stage in Treatment of Metastatic Melanoma

The promise of immunotherapy is coming to fruition with therapeutic advances in melanoma. In 1998, high-dose interleukin-2 (HD IL-2) became the first U.S. Food and Drug Administration (FDA)-approved immunotherapy for metastatic melanoma. But HD IL-2 is severely toxic and benefits only a small minority of patients. In 2011, ipilimumab became the second immunotherapy approved for metastatic melanoma. Continue reading…