New treatment regimen may decrease mortality in patients with cardiotoxicity from immune checkpoint inhibitors (Abatacept & Ruxolitinib w/ myocarditis = 3.5X survival rate over corticosteroids)

Medical Xpress / American Association for Cancer Research / Cancer Discovery ^ | Feb. 23, 2023 | Joe-Elie Salem et al

[ConservativeMind]

Among cancer patients who developed cardiotoxicity after treatment with immune checkpoint inhibitor (ICI) therapy, those treated with abatacept (Orencia), ruxolitinib, and/or mechanical ventilation as needed had a significantly lower mortality rate than those treated with standard-of-care corticosteroids.

Immune checkpoint inhibitors, in rare cases, lead to an overactive immune system that can attack muscle cells known as myocarditis when it involves the heart muscle, which occurs in approximately 1% of patients receiving ICI therapy. Patients are typically given high-dose corticosteroids.

Salem hypothesized directly targeting the autoreactive T cells may improve survival. Abatacept prevents macrophages from activating T cells and is sometimes used to help treat ICI-related myocarditis. Ruxolitinib inhibits the immune-stimulatory proteins, also decreasing T-cell activation.

While abatacept can take several weeks to reach optimal efficacy, ruxolitinib begins working almost immediately. Salem hypothesized the two could form a powerful combination in patients.

Forty consecutive cancer patients admitted with confirmed ICI-related myocarditis were evaluated in this study. The first 10 were treated according to the standard of care, including high-dose corticosteroids. The subsequent 30 patients were treated according to their disease severity and the extent of myotoxicity.

Twenty-six eligible patients in the experimental group received low-dose corticosteroids and three infusions of high-dose (20 mg/kg) abatacept. Twenty-two of the patients in this group had severe (grade 3+) myocarditis, and 17 of them were given ruxolitinib in addition to abatacept.

Ten patients met the criteria for elective ventilation, and eight were placed on a ventilator.

Results:

The rate of myotoxicity-related mortality was 60 percent among patients in the standard-of-care group and 3.3 percent among patients in the experimental treatment group.

For patients in the standard-of-care group, the overall survival rate was 20% at 6 months post-treatment. For patients in the experimental treatment group, the overall survival rate was 70 percent at 6 months post-treatment.

[ConservativeMind]

After six months, the normal corticosteroid “standard of treatment” left a 20% survival rate versus the 70% survival rate with Abatacept & Ruxolitinib.

Only 1% of immune checkpoint inhibitor users get myocarditis, but doctors need to learn this new approach to keep those people alive.

[ConservativeMind]

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