Novel Treatment Approach May Reduce Risk of Death From ICI-Related Myocarditis

A novel method of treating immune checkpoint inhibitor (ICI)-associated myocarditis may decrease the risk of death from myotoxicity, according to study results published in Cancer Discovery.

Researchers treated ICI-associated myocarditis with ruxolitinib, dose-adjusted abatacept, and screening and management of respiratory muscle involvement. Patients who received this treatment had a lower myotoxicity-related fatality rate than patients who received standard care (3.4% and 60%, respectively).

This single-center study included 40 patients with confirmed ICI-associated myocarditis. The median age of the cohort was 72 years, and 58% of patients were men. 

Most patients had genitourinary cancers (25%), lung cancer (23%), or skin cancer (23%). Three-quarters of patients received anti-PD-(L)1 monotherapy, and 25% received a combination of anti-PD-(L)1 and anti-CTLA4 therapy.

Myocarditis occurred after a median of 2 ICI doses (range, 1-3). Most patients (75%) had grade 3 or higher myotoxicity, and 39% had grade 3 or higher respiratory muscle dysfunction. 

The first 10 patients in this study were treated according to current guidelines. Initial treatment consisted of high-dose boluses of corticosteroids. In cases of cortico-resistance, second-line therapies included plasmapheresis, mycophenolate-mofetil, or low-dose abatacept. 

The treatment approach was modified for the remaining 30 patients. These patients were screened for respiratory muscle involvement and treated with mechanical ventilation if necessary. They also received ruxolitinib and abatacept. The abatacept dose was adjusted based on CD86‐receptor occupancy on circulating monocytes.

The myotoxicity-related fatality rate was 3.4% for the patients who received the modified approach and 60% among the patients managed with standard care (P <.0001). 

“Early management of respiratory muscle failure using mechanical ventilation and high‐dose abatacept with CD86 receptor occupancy monitoring combined with ruxolitinib may be promising to mitigate high fatality rates in severe immune checkpoint inhibitor myocarditis,” the researchers concluded. 

They added, however, that these results “are hypothesis‐generating and need further evaluation.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Cancer Therapy Advisor