Lower Doses of Immunotherapy for Malignant Melanoma Yield Improved Outcomes
A groundbreaking study reveals that lower doses of approved immunotherapy for malignant melanoma can lead to better tumor outcomes while minimizing side effects. This research, conducted by scientists at Karolinska Institutet and published in the Journal of the National Cancer Institute, highlights a promising approach in oncology.
The findings are particularly significant because they demonstrate that a reduced dose of immunotherapy not only reduces side effects but also enhances tumor response and extends survival. Hildur Helgadottir, the lead researcher, explains, "We've shown that a lower dose of immunotherapy drug not only causes significantly fewer side effects but also achieves better tumor outcomes and longer survival."
The traditional dose of nivolumab and ipilimumab is widely used, but it comes with a drawback: severe side effects. Sweden has started adopting a lower dose of ipilimumab, the most expensive and side-effect-prone component of this immunotherapy, to address this issue. Helgadottir notes, "In Sweden, we have the flexibility to choose doses for patients, whereas in many other countries, reimbursement policies limit them to the doses approved by drug authorities."
The study involved nearly 400 patients with advanced, inoperable malignant melanoma, the most severe form of skin cancer. The results were impressive: the regimen with a lower dose of ipilimumab showed a 49% response rate, compared to 37% for the traditional dose. Moreover, patients on the lower dose regimen experienced a median progression-free survival of nine months, compared to three months for the traditional dose. Overall survival was also significantly longer, at 42 months versus 14 months.
Serious side effects were observed in 31% of patients in the low-dose group, compared to 51% in the traditional group. Helgadottir emphasizes, "The new immunotherapies are valuable and effective, but they can also cause severe, sometimes life-threatening or chronic side effects. Our findings suggest that a lower dosage may enable more patients to endure treatment for extended periods, contributing to improved outcomes and longer survival."
Despite some differences between the treatment groups, the study's findings held even after accounting for factors like age and tumor stage. It's important to note that this is a retrospective observational study, and while it provides valuable insights, it cannot definitively establish a causal relationship.
The study was a collaborative effort between Karolinska Institutet, the Sahlgrenska Comprehensive Cancer Center at Sahlgrenska University Hospital, and funded by the Cancer Foundation, Region Stockholm, and the Radiumhemmet Research Fund.
Source: Björkström, K., et al. (2025). Evaluation of the flipped dose NIVO3+IPI1 in patients with advanced unresectable melanoma. JNCI: Journal of the National Cancer Institute. doi: 10.1093/jnci/djaf327. https://academic.oup.com/jnci/advance-article/doi/10.1093/jnci/djaf327/8372006
