A recent study from researchers at Karolinska Institutet has revealed that administering lower doses of approved immunotherapy drugs for malignant melanoma can yield improved outcomes for patients while minimizing side effects. Published in the Journal of the National Cancer Institute, the findings suggest a potential shift in treatment protocols for one of the most aggressive forms of skin cancer.
Hildur Helgadottir, a researcher at the Department of Oncology–Pathology at Karolinska Institutet and the study’s lead author, emphasized the significance of these results. “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,” she stated.
Revised Treatment Regimen in Sweden
Traditionally, the approved doses for the immunotherapies, nivolumab and ipilimumab, have been established based on rigorous clinical trials. However, due to the considerable side effects associated with these treatments, Sweden has begun to adopt a regimen that employs lower doses of ipilimumab, which is notably the most expensive component and is linked to the highest incidence of adverse effects.
“In Sweden, we have greater freedom to choose doses for patients,” Helgadottir explained, “while in many other countries, due to reimbursement policies, they are restricted by the doses approved by the drug authorities.”
Study Findings and Patient Impact
The study involved nearly 400 patients suffering from advanced, inoperable malignant melanoma. Results indicated that the lower dose regimen of ipilimumab outperformed the traditional dosing strategy. Specifically, 49% of patients in the lower dose group responded positively to treatment, compared to just 37% in the traditional group.
Moreover, the median progression-free survival—the duration patients lived without disease progression—was significantly longer for those on the lower dose, averaging nine months versus three months for the traditional dose. Overall survival rates also demonstrated a stark contrast, with patients on the lower dose living a median of 42 months compared to 14 months for those receiving the conventional dosage.
Side effects were also notably reduced; serious adverse effects were reported in 31% of patients receiving the lower dose, compared to 51% in the traditional group.
“The new immunotherapies are very valuable and effective,” Helgadottir noted, “but 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 treatment for a longer time, contributing to improved results and extended survival.”
While the study presents compelling evidence, it is essential to recognize its limitations. The findings are derived from a retrospective observational study, which means a definitive causal relationship cannot be established. Differences between treatment groups were noted, but even after accounting for factors such as age and tumor stage, the advantages of the lower dose regimen remained evident.
The full details of the study are available in the publication titled “Evaluation of the flipped dose NIVO3+IPI1 in patients with advanced unresectable melanoma,” published in 2025.
As research continues, these findings may pave the way for revised treatment strategies in the management of malignant melanoma, ultimately enhancing patient outcomes and quality of life.
