Older Patients with Metastatic Melanoma May Benefit from Immunotherapy

Age should not limit which patients with metastatic melanoma receive immunotherapy, according to a new study published in JAMA Dermatology. In fact, study findings showed that patients aged 65 years and older experienced better overall survival (OS), progression-free survival (PFS) and no greater immune-related side effects than younger patients.

The single-center cohort analysis was conducted by researchers in France to determine if age influences clinical outcomes and immune-related side effects after treatment with immunotherapy.

The researchers examined 92 patients, of which 54 were 65 years or younger and 38 were older than 65. All patients had unresectable or metastatic melanoma and were treated from January 2007 to February 2016 with Yervoy (ipilimumab), Opdivo (nivolumab) or Keytruda (pembrolizumab) — immune checkpoint inhibitors approved by the Food and Drug Administration (FDA) for treatment of late-stage melanoma.

The mean PFS was 4.8 months for patients aged 65 and older compared with 3.4 months for patients younger than 65. In the older patient group, OS was 10.1 months. However, OS was not reached in the younger patient group.

“This association between older age and a better prognosis was stronger for patients treated with anti—PD-1 compared with patients treated with ipilimumab,” the study authors wrote. Unlike Opdivo and Keytruda – which block the protein programmed cell death-1 and are more commonly referred to as PD-1 – to help the immune system kill cancer cells, Yervoy binds to a substance called CTLA-4 to help the immune system fight the disease.

“The implications of the study are that the benefits of principally anti-PD-1 therapy do not have any particular age limits and that’s both important because of melanoma’s incidence, which peaks in the 50s, in the older age patients that we see increasingly with melanoma in the clinics,” John M. Kirkwood, M.D., director of the Melanoma Center at UPMC Hillman Cancer Center in Pittsburgh, who is not an author on the study, said in an interview with CURE.

He added, “The concern that we previously had in regard to age related auto-immune disorders, including thyroid dysfunction and arthritis that are seen with age, do not seem to be associated with a loss of the benefit of these new checkpoint inhibitor therapies, which have revolutionized our treatment of melanoma.”

Investigators determined that immune-related side effects were similar in both groups. Patients were evaluated for diarrhea during treatment, reactions to the skin, thyroid modifications, hepatitis, inflammation of the pituitary gland and loss of skin color. Immune-related side effects listed as “other” were more frequent among older patients. Older patients frequently developed meningitis and immunologic nephritis (inflammation of the kidneys) than younger patients, whereas younger patients more frequently developed immunogenic interstitial pneumopathy (conditions affecting the lungs) compared with older patients.

“The clear concern for many years in oncology is that with age the immune system becomes less effective and the fact that the immune system is not as active may mean that treatments that depend upon activation of the immune system might be less effective,” Kirkwood said. “The truth is with age we haven’t documented a significant obstacle to these kinds of immune therapies on any single immune basis.”

However, more research needs to be conducted to understand the benefits of these therapies, so treatment can be tailored to patients, according to Kirkwood. He also recommended that patients learn about the different options that they have for frontline treatment and adjuvant therapy — treatment given after the primary treatment to lower the risk that the cancer will come back.

“We have moved from darkness into increasing brightness in this field of melanoma research and treatment,” Kirkwood said. “We had only 6 to 7 years ago no survival improving therapies and we now have 11 that are FDA-approved. I think we may see a time in the next year or two when that number could easily grow by time and a half over what it is today.”