Cardiac Toxicity Associated with Cancer Immunotherapy and Biological Drugs.

Andrea Montisci,Francesco Donatelli,Maria Teresa Vietri,Vittorio Palmieri,Silvia Sala,Claudio Napoli

doi:10.3390/cancers13194797

Abstract

Simple SummaryImmunotherapy is increasingly being used to treat solid tumors and lymphoproliferative diseases. The main classes of drugs are: HER-2-targeted therapies, CTLA-blockers, PD/PDL-1 inhibitors, CAR-T therapy. All these drugs are associated with meaningful cardiac toxicity, ranging from a transient decline of left ventricular function with complete reversibility to myocarditis with a high fatality rate.Cancer immunotherapy significantly contributed to an improvement in the prognosis of cancer patients. Immunotherapy, including human epidermal growth factor receptor 2 (HER2)-targeted therapies, immune checkpoint inhibitors (ICI), and chimeric antigen receptor-modified T (CAR-T), share the characteristic to exploit the capabilities of the immune system to kill cancerous cells. Trastuzumab is a monoclonal antibody against HER2 that prevents HER2-mediated signaling; it is administered mainly in HER2-positive cancers, such as breast, colorectal, biliary tract, and non-small-cell lung cancers. Immune checkpoint inhibitors (ICI) inhibit the binding of CTLA-4 or PD-1 to PDL-1, allowing T cells to kill cancerous cells. ICI can be used in melanomas, non-small-cell lung cancer, urothelial, and head and neck cancer. There are two main types of T-cell transfer therapy: tumor-infiltrating lymphocytes (or TIL) therapy and chimeric antigen receptor-modified T (CAR-T) cell therapy, mainly applied for B-cell lymphoma and leukemia and mantle-cell lymphoma. HER2-targeted therapies, mainly trastuzumab, are associated with left ventricular dysfunction, usually reversible and rarely life-threatening. PD/PDL-1 inhibitors can cause myocarditis, rare but potentially fulminant and associated with a high fatality rate. CAR-T therapy is associated with several cardiac toxic effects, mainly in the context of a systemic adverse effect, the cytokines release syndrome.

Highlights

Patients treated with either chemotherapy or radiation have a higher cancer relapse chance, and tumors may gain resistance to treatment
Immunotherapy represented a major advancement in the treatment of solid tumors and lymphoproliferative diseases
Lessons learned from anthracycline cardiac toxicity made the clinicians aware of the importance of the patients’ clinical surveillance, enrolling them in cardio-oncology programs

Summary

Introduction

Patients treated with either chemotherapy or radiation have a higher cancer relapse chance, and tumors may gain resistance to treatment. These drawbacks have encouraged the discovery of small molecules, peptides, and monoclonal antibodies for immunotherapeutic applications that stimulate the native immune defense system for cancer treatment [1] (Table 1 and Figure 1)

Adoptive T-Cell Transfer Therapy

Findings

Conclusions