Therapy consists of high-dose abatacept, ruxolitinib, and proactive monitoring for respiratory muscle involvement.
Individuals with cancer who developed cardiotoxicity after treatment with immune checkpoint inhibitor (ICI) therapy and were treated with abatacept (Orencia), ruxolitinib, and/or mechanical ventilation as needed, showed significantly lower mortality rates than those treated with standard-of-care corticosteroids, new study results indicate.
“Immunotherapy wakes up the immune system, but it sometimes wakes up autoreactive T cells that destroy your own body,” Joe-Elie Salem, MD, PhD, a professor at Sorbonne Université, said in a statement. “The heart is at the top of the list of organs you don’t want to harm.”
ICIs are a class of immunotherapeutic that release the natural “brakes” on certain immune cells, which make them more efficient at killing cancer cells.
However, this can cause an overactive immune system that can attack muscle cells, including those in the heart, in rare cases.
Investigators hypothesized that therapies directly targeting the autoreactive T cells could improve survival, including abatacept, a treatment that prevents macrophages from activating T cells, and ruxolitinib, a treatment that inhibits the immune-stimulatory proteins JAK1 and JAK2 and decreases T-cell activation.
They aimed to test if the 2 medications could form a powerful combination in individuals with severe myotoxicity.
Investigators included 40 consecutive individuals with cancer who were admitted to Assistance Publique-Hôpitaux de Paris and had confirmed ICI-related myocarditis.
The first 10 were treated with the standard of care, including high-dose corticosteroids. In the event of resistance, other immune suppressants were determined by the care team. The other 30 individuals were treated according to their disease severity and the extent of myotoxicity.
In the experimental group, 26 eligible individuals received low-dose corticosteroids and 3infuxions of high-dose (20 mg/kg) of abatacept. In the group, 22 individuals had a grade 3 or higher myocarditis, and 17 were given ruxolitinib in addition to abatacept.
All individuals in the experimental treatment group were regularly monitored for the spread of myotoxicity to the respiratory muscles to determine their eligibility for a ventilator, if necessary, where 10 met the criteria, and 8 were placed on a ventilator.
Although this is not a randomized clinical trial, the significant improvement in outcomes when patients are treated with targeted therapies is very suggestive that this regimen is helpful,” Salem said.
The rate of myotoxicity-related mortality was 60% among those in the standard-of-care group and 3.3% among those in the experimental treatment group. There was 1 myotoxicity-related death in the experimental treatment group in an individual who refused elective ventilation.
For those in the standard-of-care group, the overall survival (OS) rate was 40% at 3 months and 20% at 6 months post-treatment. For those in the experimental treatment group, the OS rate was 77% at 3 months and 70% at 6 months post-treatment.
Results of the study were published in Cancer Discovery, a journal of the American Association for Cancer Research.
Limitations of the study included a small sample size, which prevented subgroup analyses based on individual demographics and the type of ICI treatment received.
Additionally, this was not a randomized clinical trial.
New treatment regimen may decrease mortality in patients with cardiotoxicity from immune checkpoint inhibitors. EurekAlert. News release. February 23, 2023. Accessed February 24, 2023. https://www.eurekalert.org/news-releases/980264