Case Presentation: An 81 year old woman with history of stage 3 melanoma and hypothyroidism presented with a four day history of progressive weakness and dyspnea two weeks after receiving her first dose of nivolumab. Upon arrival to her local hospital, she was noted to have significantly elevated troponin level (Troponin-I > 8,000). Due to significant weakness, acetylcholine receptor antibody levels were obtained and were positive. She was subsequently started on IV methylprednisolone, IV immunoglobulin, and pyridostigmine due to concern for immune checkpoint inhibitor-induced myasthenic crisis. She showed significant improvement in weakness, but troponins remained elevated. Troponinemia was attributed to immune checkpoint inhibitor-induced myocarditis and laboratory monitoring was discontinued. After eight days, the patient was discharged to acute rehab on a prednisone taper. However, a week after discharge, she began experiencing worsening weakness and dyspnea once again, resulting in transfer to our hospital where troponins were found to be significantly elevated and IV methylprednisolone was restarted. EKG was unremarkable and echocardiogram showed normal ejection fraction, however troponins remained elevated despite appropriate steroid treatment. Given the high risk for adverse cardiac events in the setting of her myocarditis and her lack of response to steroids, she was started on abatacept and ruxolitinib. Over the course of several weeks troponin levels decreased and respiratory failure resolved. She was discharged on steroid and ruxolitinib tapers. Troponin level at subsequent follow up was negative, and the patient did not develop any adverse cardiac events over the course of her treatment.
Discussion: While rare, immune-check point inhibitor-induced myocarditis is a serious and often fatal complication that can occur even after just one dose of immunotherapy. These patients are at significant risk for major adverse cardiac events, even in the absence of impaired cardiac function on echocardiography. As the use of immunotherapy increases, inpatient providers should understand the seriousness and be prepared to treat the side effects that can accompany these medications. Early studies of the use of CTLA4 fusion protein abatacept and the JAK inhibitor ruxolitinib have shown to significantly reduce mortality in immune checkpoint inhibitor-induced myocarditis and should be considered early in the clinical course in coordination with Cardiology consultation.
Conclusions: Suspicion for cardiac involvement in the setting of immune checkpoint inhibitor-induced myotoxicity should be high and when identified, should be treated aggressively. While steroid therapy is the mainstay of treatment, this traditional approach to immune-related adverse events may not be sufficient in some cases. There are currently several second-line therapies that have shown promise in reducing mortality that should be considered early in the clinical course if a patient is not quickly improving with steroids.