• Posted December 12, 2025

Less Is More For Melanoma-Fighting Immunotherapy, Study Argues

Less might be more when it comes to immunotherapy treatment of melanoma, a new study says.

Lower doses of a drug used to treat melanoma can provide better results while reducing side effects, researchers reported Dec. 8 in the Journal of the National Cancer Institute.

“The results are highly interesting in oncology, as we show that a lower dose of an immunotherapy drug, in addition to causing significantly fewer side effects, actually gives better results against tumors and longer survival,” senior investigator Dr. Hildur Helgadottir, a senior research specialist at Karolinska Institutet in Sweden, said in a news release.

Nivolumab/ipilimumab is the most effective treatment for people with advanced melanoma, but the recommended dose can cause brutal side effects, researchers said.

Nivolumab and ipilimumab work in different ways to help the immune system better identify and aggressively attack cancer cells.

About one-third (34%) of patients quit the drug cocktail due to side effects like severe infections, neurological problems, fatigue, GI issues and rashes, researchers said in background notes.

Due to these side effects, Sweden has started treating melanoma using a lower dose of ipilimumab, which is the most expensive component of the cocktail and causes the most side effects.

This “flipped dose” contains a 3 mg per kilogram dose of nivolumab and a 1 mg per kg dose of ipilimumab, versus the standard dose of 1 mg per kg of nivolumab and 3 mg per kg of ipilimumab.

“In Sweden, we have greater freedom to choose doses for patients, while in many other countries, due to reimbursement policies, they are restricted by the doses approved by the drug authorities,” Helgadottir said.

For the new study, researchers examined the records of nearly 400 people with advanced melanoma. About half were treated with the flipped dose, and the other half with the standard dose.

Results show 49% of patients who got the flipped dose responded to the treatment, versus 37% for the traditional dose.

Progression-free survival was a median of nine months for the flipped dose versus three for the traditional dose. Overall survival also was longer, 42 months compared to 14 months. (Median means half lived longer, half for a shorter time.)

Serious side effects were seen in 31% of people taking the flipped dose, versus 51% for the standard dose.

"The new immunotherapies are very valuable and effective, but at the same time they can cause serious side effects that are sometimes life-threatening or chronic,” Helgadottir said. “Our results suggest that this lower dosage may enable more patients to continue the treatment for a longer time, which is likely to contribute to the improved results and longer survival.”

More information

The American Cancer Society has more on melanoma.

SOURCES: Karolinska Institutet, news release, Dec. 7, 2025; Journal of the National Cancer Institute, Dec. 8, 2025