Although immune checkpoint inhibitors have substantially improved clinical outcomes in many cancer types, they have also been found to induce immune-related adverse events, including myocarditis, in about 1% of patients receiving the agents, which can lead to a mortality rate of up to 50%. Current treatment of immune checkpoint inhibitor–associated myocarditis includes corticosteroids, which are not universally effective, and second-line therapies, including immunosuppressive therapies targeting T cells.
A small study investigating immune checkpoint inhibitor–associated myotoxicity in patients with cancer has found that those treated with abatacept, ruxolitinib, and/or mechanical ventilation had a significantly lower myotoxicity-related mortality rate (3.3%) compared to those treated with standard-of-care corticosteroids (60%). The clinical results are hypothesis-generating and require further evaluation, according to the study authors. These findings were published by Salem et al in Cancer Discovery.
The study investigators admitted 40 confirmed patients with immune checkpoint inhibitor–associated myocarditis to Assistance Publique-Hôpitaux de Paris. The first 10 patients were treated as per current expert consensus guidelines with high-dose corticosteroids followed by second-line agents in patients with resistance. The subsequent 30 patients were treated according to their disease severity and the extent of their myotoxicity.
Twenty-six eligible patients in the experimental group received low-dose corticosteroids and three infusions of high-dose (20 mg/kg) abatacept, a selective costimulation modulator used in the treatment of autoimmune diseases, including rheumatoid arthritis. Twenty-two of the patients in this group had severe grade ≥ 3 myocarditis, and 17 of the patients were also prescribed the kinase inhibitor ruxolitinib in addition to abatacept.
All patients in the experimental group were routinely monitored for the spread of myotoxicity to the respiratory muscles to determine eligibility for a ventilator, if necessary. Ten patients met the criteria for elective ventilation, and 8 were placed on a ventilator.
The researchers found that the rate of myotoxicity-related mortality was 60% among patients in the standard-of-care group and 3.3% among patients in the experimental treatment group. The one myotoxicity-related death in the experimental treatment group occurred in a patient who had refused elective ventilation.
For patients in the standard-of-care group, the overall survival rate was 40% at 3 months and 20% at 6 months posttreatment. For patients in the experimental treatment group, the overall survival rate was 77% at 3 months and 70% at 6 months posttreatment.
According to the study abstract, 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–related myocarditis.
“While 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,” said Joe-Elie Salem, MD, PhD, lead author of the study, a professor at Sorbonne Université, and Executive Assistant Director of Cardio-Metabolism at the Clinical Investigation Center Paris Est, in a statement. “We have to acknowledge that not all patients need the whole package. You may need all of it for the severe cases, and only some of it for intermediate cases, or even none of it for persistently asymptomatic cases. Even if it’s debated in the literature whether we should screen for and monitor the severity of every patient, for me, there’s no question.”
Disclosure: Funding for this study was provided by the Clinical Investigation Center in Paris. For full disclosures of the study authors, visit aacrjournals.org/cancerdiscovery.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.