A new 'one-two punch' method for improving checkpoint inhibitor therapy for cancers, including Hodgkin lymphoma

Medical Xpress / The Scripps Research Institute / Science ^ | June 20, 2024 | Jaroslav Zak et al

[ConservativeMind]

Checkpoint inhibitor therapies can be thought of as the molecular "brake release" for the immune system. These drugs eliminate the protein barriers that impede the immune system from recognizing and targeting cancer cells in the body. While there are multiple checkpoint inhibitors approved to treat different types of cancer, many patients don't respond or develop resistance to available regiments.

A team has now found that ruxolitinib, an approved immunosuppressive drug, supercharged T-cell responses when used alongside checkpoint inhibitors—boosting their effectiveness in fighting cancer. These findings are supported by a Phase I clinical trial of patients with Hodgkin lymphoma, as well as preclinical models.

T cells are produced by the immune system to fight off infections, as well as cancer. Patients often stop responding to checkpoint immunotherapy when their T cells begin to wane.

This phenomenon, called T-cell exhaustion, happens as T cells become chronically exposed to cancer cells. But based on the results of previous work, Teijaro and his research team wondered whether a JAK inhibitor—like ruxolitinib—could increase T-cell production, while also improving checkpoint inhibitors and their "brake release" effects.

JAK inhibitors restrict signals believed to cause inflammation, resulting in the immune system "calming down."

The team initiated a Phase I clinical trial of 19 patients with Hodgkin lymphoma who failed to respond to checkpoint inhibitors or relapsed following an initial response.

"Among patients with all types of cancer, fewer than 20% respond to checkpoint inhibitors," explains Jaroslav Zak.

But two years after starting a treatment regimen that combined ruxolitinib with the checkpoint inhibitor nivolumab—a current standard of care—87% of patients were still alive, and 46% stopped exhibiting signs of cancer progression altogether.

[ConservativeMind]

46% had halted any cancer progress, even two years later, by adding ruxolitinib (Jakafi).

[ConservativeMind]

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[Bigg Red]

FTA: ...available regiments...

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What?!

Soldier on.