CARDiac Toxicity Following ImmunOtherapy Treatment for Melanoma

Primary aim • To establish the feasibility of conducting a study to investigate late cardiac side effects caused by immunotherapy in patients with melanoma in order to generate data to support a larger study in this patient population.

Secondary aims

• To assess factors impacting on the acceptance and adherence with cardiac investigations.
• To contribute to the understanding of long-term cardiac toxicities following immunotherapy which will enable their early recognition.

Primary endpoint

• Acceptance rate (reported as the total number of patients consented divided by the number of patients invited for the study).

Secondary endpoints

• Adherence rate (reported as the proportion of patients completing all the scheduled cardiac screening tests divided by the number of patients enrolled in the study).
• Recruitment rate (reported as the number of patients recruited on average per month in each site, and overall).
• Reasons for non-adherence or declining to consent.
• Difference in adherence rates between adjuvant early disease setting and metastatic setting.
• Proportion of patients who experience cardiac irAEs during long-term follow-up, post-treatment.
• Prevalence of cardiac irAEs.

The planned sample size is 60 participants.

The project will assess 3 groups of patients at different timepoints during their standard of care surveillance, at 2-4, 5-7 and 8-10 years following the completion of their immunotherapy treatment for melanoma. Patients on routine follow-up, at 2 to 10 years following the completion of immunotherapy treatment for melanoma will be identified by searching through database of patients with melanoma who received immune checkpoint inhibitors (ICI). Patients respecting the inclusion criteria will be invited to take to part to the study.

Patients included in the study will undergo screening blood tests including cardiac biomarkers (troponin I, NTproBNP, lipid profile, HbA1c, ferritin), a 12 lead ECG and transthoracic echocardiography, a cardiac MRI alongside completing a questionnaire about cardiac events and risk factors. Patients will have blood tests done at Royal Marsden or Royal Free, while all the other cardiac investigations (ECG, transthoracic echocardiography, cardiac MRI) will be performed at the Royal Brompton Hospital. Surveillance imaging performed as per standard of care at the Royal Marsden or at the Royal Free will be reviewed for evidence of atherosclerosis by the team at the Royal Brompton. The cardiology team at the Royal Brompton will review cardiac investigations' results and abnormal results will be flagged.

A summary report will be generated and sent to the patients, their GPs, and the Site irrespective of the results found, and abnormal results will be investigated as per standard of care. The prevalence of cardiac adverse events will be summarised.

Inclusion criteria

• Written informed consent
• Age 18 years or older
• Confirmed diagnosis of melanoma
• Stage IIB or IIC or stage III or stage IV melanoma
• Previous immunotherapy with immune-checkpoint inhibitors (anti PD-(L)1 +/- anti CTLA-4) for melanoma
• On standard of care surveillance, at 2 to 10+ years following the completion of immunotherapy treatment

Exclusion criteria

• Medical or psychological condition that would preclude informed consent.
• Known contraindications to MRI, such as claustrophobia, pregnancy, or indwelling metallic implant which is not MR conditional
• Current active treatment with systemic therapy for any malignancy.
• Active treatment with systemic therapy for any malignancy started after the completion of immunotherapy for melanoma.
• Subjects unable to comply with the study or sample schedule.
• Planned participation in a drug trial receiving investigational agents.