Background: Ibrutinib has revolutionized treatment for several B-cell malignancies. However, a recent clinical trial where ibrutinib was used in front-line setting showed increased mortality during treatment compared to conventional chemotherapy. Cardiovascular toxicities were suspected as the culprit but not directed assessed in the study. Objective: We aimed to identify and characterize cardiovascular adverse drug reactions (CV-ADR) associated with ibrutinib. Methods: We utilized VigiBase (International pharmacovigilance database) and performed a disproportionality analysis using reporting odds-ratios (ROR) and information component (IC) to determine whether CV-ADR and CV-ADR deaths were associated with ibrutinib. IC compares observed and expected values to find associations between drugs and ADR using disproportionate Bayesianreporting; IC025 (lower end of the IC 95% credibility interval)> 0 is significant. Results: We identified 303 ibrutinib-associated cardiovascular deaths. Ibrutinib was associated with

Immune-checkpoint-inhibitor (ICI)-associated myotoxicity involves the heart (myocarditis) and skeletal muscles (myositis), which frequently occur concurrently and is highly fatal. We report the results of a strategy that included identification of individuals with severe ICI-myocarditis by also screening for and managing concomitant respiratory muscle involvement with mechanical ventilation, as well as treatment with CTLA4-fusion protein abatacept and the Janus-kinase inhibitor ruxolitinib. Forty cases with definite ICI-myocarditis were included with pathological confirmation of concomitant myositis in the majority of patients. In the first 10 patients, using recommended guidelines, myotoxicity-related fatality occurred in 60%, consistent with historical controls. In the subsequent 30 cases, we instituted systematic screening for respiratory muscle involvement coupled with active ventilation and treatment using ruxolitinib and abatacept. Abatacept dose was adjusted using CD86-receptor occupancy on circulating monocytes. Myotoxicity-related fatality rate was 3.4%(1/30) in these 30 patients vs.60% in 1st quartile(p<0.0001). These clinical results are hypothesis-generating and need further evaluation.