Lower dosing in melanoma treatment increases efficacy and safety

Treating malignant melanoma with lower doses of approved immunotherapy appears to result in improved results, while also reducing side effects. Investigators from the Karolinska Institutet in Stockholm, Sweden reported these findings on Dec.8, 2025 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 tumours and longer survival,” said lead investigator and author Hildur Helgadottir, MD, PhD, a researcher at the Department of Oncology-Pathology at Karolinska Institutet, in Stockholm, Sweden.

In 2016 the combination therapy of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (NIVO1+IPI3) was approved for the treatment of advanced melanoma.

Since then, results from the CheckMate 511 trial have showed improved treatment tolerability with the use of a flipped dose, NIVO3+IPI. However, this regimen has not yet been approved for treating melanoma.

For this new study the investigators recruited 399 subjects with advanced unresectable melanoma treated with NIVO3+IPI1 or NIVO1+IPI3.

Treatment with a lower dose of ipilimumab was more effective, with 49% of the subjects responding to treatment, compared with 37 percent of those treated with the traditional dosing.

Progression-free survival was a median of nine months for the lower dose, compared to three months for the traditional dose.

Overall survival was 42 months for the lower dose compared to 14 months for the traditional dose.

Notably, serious side effects appeared in 31 percent of subjects in the low-dose group compared to 51 percent in the traditional group.

“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. 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,” said  Helgadottir.