Using a lower dose of melanoma immunotherapy may extend survival while reducing dangerous side effects.
New research suggests that reducing the dose of a commonly used immunotherapy for malignant melanoma may actually improve treatment results while lowering the risk of side effects. Scientists at Karolinska Institutet reported the findings 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,” says last author Hildur Helgadottir, a researcher at the Department of Oncology-Pathology at Karolinska Institutet, who led the study.
Why Sweden Adjusted the Standard Dose
The established and approved treatment for advanced melanoma combines nivolumab and ipilimumab at specific standard doses. However, because this regimen is often linked to significant side effects, Swedish doctors have increasingly adopted a strategy that reduces the amount of ipilimumab. This drug is the costliest component of the combination therapy and is also responsible for many of its most severe adverse reactions.
“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,” says Hildur Helgadottir.
Higher Response Rates and Longer Survival
The study followed nearly 400 people with advanced, inoperable malignant melanoma, the most serious type of skin cancer. Results showed that patients receiving the lower dose of ipilimumab responded better to treatment. In that group, 49 percent of patients experienced a measurable response, compared with 37 percent among those who received the traditional dose.
Progression-free survival, meaning the length of time patients lived without their disease worsening, reached a median of nine months in the lower-dose group. Patients treated with the standard dose had a median of three months. Overall survival also differed substantially, with patients in the reduced-dose group living a median of 42 months compared with 14 months in the traditional-dose group.
Fewer Serious Side Effects
Severe side effects occurred in 31 percent of patients given the lower dose, while 51 percent of those receiving the conventional regimen experienced serious complications.
“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,” says Hildur Helgadottir.
Study Design and Collaboration
Although some baseline differences existed between the two patient groups, the improved outcomes linked to the lower dose remained even after researchers accounted for factors such as age and tumor stage. Because the research was a retrospective observational study, it cannot prove a direct cause-and-effect relationship.
Reference: “Evaluation of the flipped dose NIVO3+IPI1 in patients with advanced unresectable melanoma” by Karl Björkström, Cissi Liu, Anna Fager, Lisa L Liu, Lars Ny and Hildur Helgadottir, 8 December 2025, JNCI: Journal of the National Cancer Institute.
DOI: 10.1093/jnci/djaf327
The project was carried out in partnership with the Sahlgrenska Comprehensive Cancer Center at Sahlgrenska University Hospital. Funding was provided by the Cancer Foundation, Region Stockholm, and the Radiumhemmet Research Fund.
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