Mitigating Cardiotoxicity Resulting from Immune Checkpoint Inhibitor Therapy

In season 4, episode 9 of Targeted Talks, Kerry Reynolds, MD, clinical director, inpatient oncology units, director, Severe Immunotherapy Complications Program, Massachusetts General Hospital, discusses the occurrence of myocarditis in patients with cancer treated with immune checkpoint inhibitors (ICIs).

According to Reynolds, ICIs are used for the treatment of more than 20 forms of cancer and very effective. However, approximately 1.0% to 1.23% of patients will develop myocarditis. Reynolds explains that myocarditis is a severe adverse event (AE), and it is important to collect evidence on this AE and develop an agent to treat it.

Reynolds and fellow investigators looked at the immunomodulating agent, abatacept (Orencia), for the treatment of ICI-associated myocarditis in a phase 3, investigator-initiated, randomized, placebo-controlled study (ATRIUM; NCT05335928). The trial in progress seeks to confirm that abatacept could lessen the risk of cardiac immune activation and improve survival, as demonstrated preclinically. Reynolds presented the study design during the American Society of Clinical Oncology (ASCO) Annual Meeting.¹

“This is really a collaborative study because we have a cancer patient that had a cancer drug but developed a cardiovascular event. And I think one of the hearts to know about working in this field is that it really takes collaboration from both oncologists and sub specialists. So, even the trial was designed so that we work as a team for cardiology and oncology,” explains Reynolds about the ATRIUM study.

ATRIUM will include about 390 hospitalized patients with ICI-associated myocarditis. Patients will be treated with abatacept 10 mg/kg or placebo. Investigators of the study will observe patients for the rates of major adverse cardiac events, which is the primary end point of the study. The secondary end points of the study include rate of cardiovascular death, non-fatal sudden cardiac arrest, cardiogenic shock, significant ventricular arrhythmia, significant bradyarrhythmia, or incident heart failure, severity of myocarditis, increase in serum troponin levels, clinical status after infusion at key timepoints, the proportion of patients with Fatal and non-fatal deep vein thrombosis and pulmonary embolism, and the rate of other immune-related AEs between the 2 arms.²

“The enrollment has started, which is great. Multiple sites have enrolled, so it's really starting to pick up. It's a five year study, so in the coming year or so, we suspect that the numbers will increase,” says Reynolds, regarding the status of the study.

_REFERENCES:

_{1. Reynolds KL, Zlotoff DA, Mooradian M, et al. Abatacept for immune checkpoint inhibitor associated myocarditis (ATRIUM): Phase 3, investigator-initiated, randomized, placebo-controlled study to evaluate the efficacy and safety of abatacept compared to placebo in hospitalized patients with immune checkpoint inhibitor associated myocarditis. J Clin Oncol. 2023;41(suppl 16): TPS2680-TPS2680. doi: 10.1200/JCO.2023.41.16_suppl.TPS2680}

_{2. Abatacept in immune checkpoint inhibitor myocarditis (ATRIUM). ClinicalTrials.gov. Updated March 17, 2023. Accessed June 30, 2023.}