(017) Immune Checkpoint Inhibitors and Overlap Syndrome of Myocarditis and Myositis or Myasthenia Gravis: Analysis of WHO VigiBase Database.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of various malignancies. Despite their efficacy, ICIs may lead to the development of immune-related adverse events (irAEs). The overlap of irAEs, particularly the concurrence of dual conditions of myositis, myasthenia gravis, and myocarditis. Therefore, we used the WHO global database of individual case safety reports to understand clinical complexity of these cases.

Objectives: Describe concurrence of myocarditis and myositis or myasthenia Gravis associated with ICIs in VigiBase.

Methods: VigiBase was accessed on January 2023 and used to extract data for ICI-treated patients with myositis or myasthenia gravis reactions co-occurring with myocarditis. Patients were categorized into two groups: Single M (1M) of myositis or myasthenia gravis or myocarditis, and dual M (2M); which included patients with two adverse events of the three. The Pearson Chi-squared test, Wilcoxon rank-sum/ANOVA test, and log-rank test were used to compare categorical, continuous, and time-to-event data, respectively.

Results: A total of 1,623 patients with irAEs due to ICI therapy, 64% were male and 36% female, with a median age of 70. The majority fell into the age groups over 70 (628:50%). Most patients were on ICI monotherapy (74%). The most common cancers treated were lung cancer (471:33%). Myositis was the most prevalent condition (1199:74%), followed by myasthenia gravis at 589 (36%) and myocarditis at 255 (16%). Patients with only (1M) constituted (1,203:74%), while those with (2M) were (420:26%). Fatal outcomes were reported in (282:17.4%) of cases. The occurrence of myocarditis was exclusive to the 2M group, with a striking 61% prevalence, indicating a possible association between dual conditions and the development of myocarditis. Furthermore, there was a notable increase in myasthenia gravis cases in the 2M group (53%) compared to the 1M group (30%). While myositis was present in 86% of the 2M group, which was significantly higher than the 70% in the 1M group. Cases with 2M were more reported in renal cancer patients compared to those with 1M, at rates of 22% and 14% respectively. Conversely, lung cancer was less common in the 2M group (44%) compared to the 1M group (35%), with a statistically significant p-value of 0.005.
In 2M patients, there was a notable increase in fatal outcomes 56% of patients with a significant increase compared to 44% with 1M, p-value < 0.001.

Conclusions: This is the largest dataset demonstrating that duel M is associated with a significantly higher mortality than single M especially in cases with renal cancer. These data indicate the need to further study to identify temporal relationships, underlying risk factors, employ early immunosuppressive approaches to improve patient outcomes.