Researchers Urge Caution of Immunotherapy in Older Patients with Melanoma

An expert told CURE® that immunotherapy may come with a wide range of unpredictable side effects.

For patients with melanoma aged 75 and older, adjuvant (postsurgical), treatment with immune checkpoint inhibitors should be used with precaution, researchers have stated, citing relatively less efficacy and higher risk of toxicity when compared with younger patients. However, one expert who spoke with CURE® disputed these findings.

A team of German researchers whose findings were published in Cancer Immunology, Immunotherapy, compared 339 patients younger than 75 with 117 patients who were 75 and older, retrospectively analyzing immune-related side effects and outcomes for patients treated with immune checkpoint inhibitors Keytruda (pembrolizumab) or Opdivo (nivolumab) between Jan. 1, 2018 and Dec. 20, 2022.

Researchers reported that treatment was well-tolerated in both patient groups, with no significant difference in the overall occurrence of side effects.

Regarding notable mild to moderate side effects for patients 18 to 74 and 75 and older, respectively, rates of skin toxicity were 17.4% and 30%; rates of fatigue were 15.7% and 6.8%; rates of colitis (inflamed reaction in the colon) and diarrhea were 3.6% and 7.7%; and rates of nephritis (kidney inflammation)/elevated creatine kinase were 2.1% and 6.8%.

Furthermore, regarding disease-free survival, the median time between the start of immune checkpoint inhibitor therapy and the occurrence of disease metastasis was nine months among the older patients and 14 months among the group of younger patients.

“In terms of efficacy, it has to be noted that [disease-free survival] was significantly shorter in the elderly cohort,” researchers wrote. “There was also significantly more skin and nephrological toxicity and more cases of colitis/diarrhea. According to our results, adjuvant [immune checkpoint inhibitors [should be used with precaution in patients aged [at least] 75 years [old].”

Learn more about melanoma: Presurgical, Postsurgical Targeted Therapy Effective in Some Melanomas

But Dr. Siwen Hu-Lieskovan, Associate Professor of Medicine, and Director of Solid Tumor Immunotherapy at the Huntsman Cancer Institute, University of Utah, didn’t agree with the researchers’ conclusion, taking issue with the size of the study’s patient population.

“It's a relatively small cohort,” she said. “If you're going to explore toxicity in elderly patients in the general population, to have a little bit over 100 patients in this cohort, it's really a very small sample to look at. Especially when we're talking about toxicity to immunotherapy, it can be a very different set of symptoms, and different organs get involved. So when you lump everything together, it's really prone for sampling error.”

Immunotherapy — such as Keytruda or Opdivo — is a type of cancer treatment that helps a patient’s immune system fight cancer, as the National Cancer Institute explained. Both drugs are known as PD-1 inhibitors and they allow T cells, part of the body’s immune system, to kill cancer cells.

Such treatments, Hu-Lieskovan said, come with a wide range of unpredictable side effects.

“In general, the toxicity to immunotherapy is very unpredictable, in terms of which organ is going to be evolved and when,” she said. “So, a problem was managing toxicity to immunotherapy, and with anti-PD-1 therapy, it's actually a little better because only 10% to 20% of patients get severe toxicity. Most patients actually can tolerate the treatment pretty well with no problems or just mild problems. The toxicity to immunotherapy is ultimately immune in nature. So, the cells were trying to activate the anti-tumor immune response or reactivate it, but in the process, the immune cells start to attack the normal cells and in each individual patient, and we actually cannot predict which organ is going to be affected.”

Researchers reported that 57.3% of older patients prematurely discontinued treatment with immune checkpoint inhibitors, versus 32.1% of younger patients.

“[Older] patients are treated with [fewer] doses, and they discontinue their treatment much earlier than the younger patients,” said Hu-Lieskovan. “That could explain why this population had relapsed disease — not because of all these toxicities, or differences in terms of efficacy.”

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