Combining immunotherapy with other cancer treatments in patients with malignant melanoma can improve outcomes, but is associated with increased side effects. Now, researchers at Vienna General Hospital Comprehensive Cancer Center are testing novel combinations in two upcoming studies, aiming to improve the therapy side-effect profile.

The American Cancer Society estimates that in 2016 more than 76,000 people will be diagnosed with melanoma and nearly 10,000 will die from the disease in the U.S. alone. For the past few years, immunotherapy has significantly improved the survival rates of patients with metastatic melanoma compared to conventional chemotherapy regimens, but the results still require improvement.

“New data show that 50% of patients with metastasizing melanomas who receive immunotherapy are still alive after 3 years — and indeed with a good quality of life,” Christoph Höller of the Department of Dermatology and Venerology at MedUni Vienna and Vienna General Hospital and member of the Comprehensive Cancer Center, said in a press release. “However, this also means that it works less well, if at all, for the other 50%. We are therefore looking for new ways to bring about further improvements in this success rate,” he said.

Results from a large-scale, multi-center study, presented in June at the American Society for Clinical Oncology (ASCO) Congress, showed that combining two immune checkpoint inhibitors can further improve patients’ outcomes. But the treatment also shows greater side effects, such as diarrhea, skin rashes and severe fatigue.

“This is where our concepts come in and we will be testing them over the coming years,” Höller said, adding that he and colleagues now will test other immunotherapy drug combinations that can not only improve patients’ outcomes, but simultaneously control or reduce treatment-related side effects.

“One study has just started,” Höller said. “It is being conducted in collaboration with the MedUni Vienna and Vienna General Hospital Department of Medicine I, and we are testing a new combination of two immune checkpoint inhibitors, the antibodies against PD-1 and LAG-3. The other study, which is about to start, is looking at whether better results can be achieved by combining the PD-1 antibody with a specially modified virus.”

LAG-3 inhibitors have emerged as promising immune checkpoint inhibitors that, similar to PD-1 and CTLA-4 inhibitors (such as Opdivo, Keytruda, and Yervoy), remove the breaks on immune cells, allowing them to better recognize and kill cancer cells.

With the advances in combined therapies, researchers hope that, in the long term, the majority of patients with melanoma will be cured, or that the disease at least will be transformed into a chronic one.

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