A recent study from researchers at Karolinska Institutet indicates that administering lower doses of approved immunotherapy drugs for malignant melanoma may yield improved outcomes for patients. This groundbreaking research, published in the Journal of the National Cancer Institute, reveals not only better tumor response rates but also a reduction in adverse side effects associated with treatment.
Hildur Helgadottir, the lead researcher from the Department of Oncology–Pathology at Karolinska Institutet, emphasized the significance of the findings. “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,” she stated.
Lower Dose Regimen in Sweden
In Sweden, the traditional dosing regimen for the immunotherapy drugs nivolumab and ipilimumab has been under scrutiny due to the extensive side effects experienced by patients. The country has increasingly adopted a treatment approach utilizing lower doses of ipilimumab, which is the most costly component of this combination therapy and has been linked to severe side effects. Dr. Helgadottir explained, “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.”
Study Results and Patient Outcomes
The study analyzed nearly 400 patients diagnosed with advanced, inoperable malignant melanoma, the most severe form of skin cancer. Results demonstrated that the lower dose regimen of ipilimumab was associated with a higher response rate. Specifically, 49% of patients treated with the lower dose responded positively, compared to just 37% for those receiving the standard dosage.
Progression-free survival, which measures the duration patients live without disease worsening, was significantly longer for those on the lower dose, with a median of nine months compared to three months for the traditional dose. Additionally, overall survival rates improved, with patients on the lower dose living for an average of 42 months versus 14 months for those on the conventional treatment.
The incidence of serious side effects was also notably lower, affecting 31% of patients receiving the lower dose compared to 51% in the traditional group.
Dr. Helgadottir noted the implications of these findings, stating, “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.”
While the study’s findings are promising, it is important to acknowledge its limitations. The research is classified as a retrospective observational study, which means that a direct causal relationship cannot be definitively established. Differences in patient characteristics between the two treatment groups were noted; however, adjustments for factors such as age and tumor stage still showed improved outcomes for those receiving lower doses of ipilimumab.
For further information, the study is detailed in the article titled “Evaluation of the flipped dose NIVO3+IPI1 in patients with advanced unresectable melanoma,” published in the Journal of the National Cancer Institute in 2025. The DOI for the research is 10.1093/jnci/djaf327.
