Abstract 1581P
Background
Immune checkpoint inhibitors (ICIs) have revolutionized the management of multiple tumors, due to improved efficacy, quality of life and safety. While most immune-related adverse events (irAEs) are mild and easily managed, in rare cases such events may be life-threatening, especially those affecting the neuromuscular and cardiac system. The management of neuromuscular/cardiac irAEs is not clear due to the lack of consistent data. Therefore, we performed a pooled analysis of collected cases from selected Italian centers and individual data from published case reports and case series, in order to improve our understanding of these irAEs.
Methods
We collected retrospective data from patients treated in 6 Italian centers with ICIs (PD-1 or PD-L1 and/or CTLA-4 inhibitor) for any solid tumor who experienced neuromuscular and/or cardiovascular toxicity. Then, to increase the caseload, we performed a search of case reports and series of neuromuscular/cardiac irAEs from ICIs with any solid tumor.
Results
Our analysis includes cases from our institutions (n=18) and the case reports identified in our systematic literature search (n=112), for a total of 130 patients. Among these patients, 44 had complete resolution of their neuromuscular/cardiac irAEs, in 21 there was a clinical improvement with mild sequelae, and 52 patients died as a result of the irAEs. Factors significantly associated with worse outcomes were the earlier irAE onset, within the first 2 cycles of ICI (Fisher P< 0.0001), clinical manifestation of both myositis and myocarditis if compared to patients who developed only myositis or myocarditis (Chi-square P= 0.0051), increased peak troponin value ((Mann-Whitney P= 0.0346) and the development of arrythmia (Fisher P= 0.0051).
Conclusions
To our knowledge, this is the widest collection of individual cases of immune-related myocarditis/myositis. Early irAE onset, concurrent development of myositis and myocarditis, increased peak troponin value and occurrence of arrythmias are associated with worse outcomes and should encourage an aggressive immunomodulatory treatment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Italian Ministry of Health.
Disclosure
E.T. Tanda: Financial Interests, Institutional, Invited Speaker: BMS, MSD. F. Spagnolo: Financial Interests, Institutional, Invited Speaker: Sanofi Genzyme, Roche, BMS, Novartis, Merck, SunPharma, MSD, Pierre Fabre; Financial Interests, Institutional, Advisory Board: Novartis, Philogen, SunPharma, MSD. G. Barletta: Financial Interests, Institutional: AstraZeneca, Roche, Boeringher Inghelaim, Pierre Fabre, BMS. F. de rosa: Financial Interests, Institutional: MSD, Sun Pharma, Pierre Fabre, Novartis, BMS. R. Marconcini: Financial Interests, Personal, Advisory Board: novartis, Ipsen, BMS, MSD; Financial Interests, Personal, Invited Speaker: Novartis, Ipsen, BMS, MSD, Pierre Fabre, Sanofi. L. Del Mastro: Financial Interests, Personal, Invited Speaker, Educational meeting: Novartis, Symposia, Andromeda E20, Vyvamed srl; Financial Interests, Personal, Invited Speaker, Lecture: Ipsen; Financial Interests, Personal, Advisory Board, Her2+ and TN breast cancer: Roche; Financial Interests, Personal, Invited Speaker, Consultancy for TNBC text: Roche; Financial Interests, Personal, Advisory Board, denosumab: Amgen; Financial Interests, Personal, Advisory Board, Early and metastatic BC: Eli Lilly; Financial Interests, Personal, Invited Speaker, CDK4-6 inhibitors: Eli Lilly; Financial Interests, Personal, Advisory Board, tucatinib: Seagen Int; Financial Interests, Personal, Advisory Board, Oncotype dx: Exact sciences, Havas life; Financial Interests, Personal, Advisory Board, Neratinib: Pierre Fabre; Financial Interests, Personal, Invited Speaker, Internal training: MSD; Financial Interests, Personal, Invited Speaker, Educational meetings: Accademia Nazionale Medicina; Financial Interests, Personal, Invited Speaker, Author for BC text: Pensiero Scientifico Editore; Financial Interests, Personal, Advisory Board, Breast cancer: Uvet; Financial Interests, Personal, Author slide kits and interviews: Think2it; Financial Interests, Personal, Advisory Board, Palbociclib: Pfizer; Financial Interests, Personal, Invited Speaker, Breast cancer: Aristea, Meeting SrL; Financial Interests, Personal, Author slide kits: Forum service; Financial Interests, Personal, Author text about biosimilars: Edizioni Minerva Medica; Financial Interests, Personal, Consultant: Kardo srl; Financial Interests, Personal, Invited Speaker, Breast cancer meetings: Delphi international, Over srl; Financial Interests, Personal, Invited Speaker: Prex Srl, Editree; Financial Interests, Personal, Advisory Board: Uvet, Collage SpA, Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Interview: Infomedica srl; Financial Interests, Personal, Consultant: Sharing progress in cancer care - Switzerland; Financial Interests, Institutional, Funding, National coordinating PI: Roche; Financial Interests, Institutional, Funding, Local PI: AstraZeneca, Roche, Eli Lilly, Daiichi Sankyo, Novella Clinical, Novartis; Non-Financial Interests, Institutional, Product Samples, Genomic Test: FoundationOne. C. Genova: Financial Interests, Institutional: AstraZeneca, BMS, Boehringer Ingelheim, MSD, Roche, Takeda, ThermoFisher, Sanofi; Financial Interests, Institutional, Research Grant: BMS, Italian Ministry of Health. All other authors have declared no conflicts of interest.