Lower Immunotherapy Doses Show Promise in Melanoma Treatment, Study Finds
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A new study suggests that reduced doses of immunotherapy could offer improved outcomes and fewer side effects for patients battling advanced melanoma. Published in the Journal of the National Cancer Institute by researchers at Karolinska Institutet, the findings challenge conventional treatment protocols and offer a potential path toward more tolerable and effective cancer care.
The research, conducted on nearly 400 patients with advanced, inoperable malignant melanoma – the most dangerous form of skin cancer – reveals a significant benefit from a lower dosage regimen of the immunotherapy drugs nivolumab and ipilimumab. According to a researcher who led the study, “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.”
Sweden’s Pioneering Approach
Currently, the standard treatment involves a specific, approved dose of both nivolumab and ipilimumab. However, due to the often-severe side effects associated with these drugs, Sweden has increasingly adopted a strategy of utilizing a lower dose of ipilimumab – the more expensive component and primary driver of 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,” explained the researcher. This flexibility allowed for the observation of the benefits associated with the adjusted dosage.
Improved Outcomes with Lower Doses
The study demonstrated a clear advantage for the lower-dose ipilimumab regimen. Nearly half (49%) of patients responded to treatment, a notable increase compared to the 37% response rate observed with the traditional dose. Furthermore, patients receiving the lower dose experienced significantly longer periods without disease progression, with a median of nine months compared to just three months in the traditional dose group.
Perhaps most strikingly, overall survival was substantially extended – 42 months with the lower dose versus 14 months with the standard dose. The reduction in side effects was also substantial, with 31% of patients in the low-dose group experiencing serious adverse events, compared to 51% in the traditional group.
Balancing Efficacy and Tolerability
Immunotherapies represent a major advancement in cancer treatment, but their potential for serious, even life-threatening, side effects remains a significant concern. The study’s findings suggest that a lower dosage may allow more patients to continue treatment for a longer duration, ultimately contributing to improved outcomes and extended survival.
“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,” the researcher stated.
While the study accounted for factors like age and tumor stage, and the positive impact of the lower dose remained consistent, researchers acknowledge its limitations. As a retrospective observational study, it cannot definitively prove a causal relationship between the dosage and the observed outcomes. Further research, including prospective clinical trials, will be crucial to confirm these findings and establish new treatment guidelines.
More information: Evaluation of the flipped dose NIVO3+IPI1 in patients with advanced unresectable melanoma, JNCI Journal of the National Cancer Institute (2025). DOI: 10.1093/jnci/djaf327, doi.org/10.1093/jnci/djaf327.
