Background Immune checkpoint inhibitor (ICI) associated cardiotoxicity is a rare but serious immune related adverse event (irAE) that occurs in <1% of patients (pts), and literature on IO re-challenge in these patients remains sparse.

Methods We performed a retrospective review study of pts treated with IO at the University of Virginia Comprehensive Cancer Center between 2012–2023 and developed cardiotoxicity. We analyzed in detail the demographics, disease characteristics, management of irAE, impact on cancer treatment, rates of IO re-challenge and clinical outcomes of patients.

Results Of a total of 1979 pts, 9 experienced CTCAE v5 ≥grade(G)1 cardiotoxicity. Median age was 69 years, 78% were male and 78% were white. The most frequent cancers were lung (44%), melanoma (22%), endometrial (11%), genitourinary (11%), and head-neck cancers (11%). 78% (n=7) received single agent anti-PD1 and 22% (n=2) received combination IO. Most common cardiotoxicities were myocarditis in 5 (56%), cardiogenic shock in 4 (44%), and arrhythmias in 3 (33%) pts. Most common ≥G3 cardiotoxicity was hypertropinemia, seen in 6 pts (67%). Median number of IO infusions prior to cardiotoxicity was 3 (IQR 2 to 5). Intent of IO was adjuvant in 6 (67%) and palliative in 3 pts (33%). All pts needed hospitalization. 2 pts (22%) had early onset cardiotoxicity (within 30d). Troponin-I elevation was seen in 67% (n=6), BNP elevation in 67% and CK in 33% (n=3) pts. ECG abnormalities were seen in 75% (n=7), most commonly atrial fibrillation, new RBBB, and ST elevations. ECHO abnormalities were seen in 78% (n=7), most commonly reduced ejection fraction and pericardial effusion. Cardiac MR abnormalities were seen in 80% (n=4/5) pts who underwent cardiac MR. IO was interrupted in all pts at cardiotoxicity onset, and permanently discontinued in 6 (67%). All pts received pulse dose IV steroids. Additional irAEs were seen in 3 patients (33%), all of which occurred prior to cardiotoxicity. IO was resumed in 2 (22%) pts for a median of 35 cycles. At the time of cardiotoxicity onset, best disease response was SD in 2 (22%), PR in 3 (33%) and PD in 4 pts (44%). At a median follow up of 32 months, 89% (8/9) pts had died, all from disease progression.

Conclusions ICI-associated cardiotoxicity is a rare but serious complication with poor prognosis, as occurrence of cardiotoxicity often necessitates IO discontinuation. IO re-challenge may be attempted in carefully selected cases on an individual basis.

Ethics Approval This study was approved by the institutional review board of the University of Virginia with the HSR number 24436.