26 June 2024

An immunosuppressant drug can “supercharge” checkpoint inhibitor therapy for Hodgkin’s lymphoma, researchers have reported.

The new combination is backed by both a phase I clinical trial and by preclinical studies.

The research involved the JAK inhibitor ruxolitinib – originally approved for treatment of graft versus host disease, and designed to restrict signals linked to inflammation to calm the immune system.

Researchers at the Scripps Research Institute, California, wondered whether it might restore the function of exhausted T cells, and so improve immune checkpoint inhibitor therapy.

Animal studies involving mice found that adding ruxolitinib to the checkpoint inhibitor nivolumab also increased the number of natural killer cells.

In a phase I trial the treatment combination has been tested on 19 patients recruited by the University of Minnesota, USA. 87% of patients were alive two years after starting treatment and, the researchers report, 46% ceased to show signs of cancer progression.

The study has also shown the patients enjoyed a reduction in myeloid suppressor cells, which can contribute to cancer.

Researcher Dr Jaroslav Zak said: “Anecdotally, we know for sure that at least one patient had a very good response that lasted beyond the two years of the clinical trial. Unlike chemotherapy, this treatment didn’t just slow down the disease but actually reversed it.”

Source:

Zak J, Pratumchai I, Marro BS, Marquardt KL, Zavareh RB, Lairson LL, Oldstone MBA, Varner JA, Hegerova L, Cao Q, Farooq U, Kenkre VP, Bachanova V, Teijaro JR. (2024) “JAK inhibition enhances checkpoint blockade immunotherapy in patients with Hodgkin lymphoma.” Science, 21 June 2024, doi: 10.1126/science.ade8520

Link: https://www.science.org/doi/10.1126/science.ade8520

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