Intralesional immunotherapy as a strategy to treat melanoma

ABSTRACT

Introduction: Intralesional immunotherapy supplements systemic treatments and often achieves higher remission rates as compared to systemic therapy. Its indication is metastatic melanoma with limited tumor burden, particularly in loco-regional metastasis and distant soft tissue metastasis.

Areas covered: This review describes intralesional immunotherapy with talimogene laherparepvec (T-VEC), with velimogene aliplasmid (Allovectin-7) and with intralesional interleukin-2. These therapies function exclusively by activating the immune system. Furthermore, Rose Bengal and electrochemotherapy have been included, as bystander effects have been observed with these treatments.

Expert opinion: Objective remissions are achieved in a higher percentage with intralesional immunotherapies, such as intralesional interleukin-2 with up to 69% of complete remissions, as compared to systemic treatment. Therefore, intralesional immunotherapy may act as supplement in the armament against metastatic melanoma. In particular, for patients with multiple cutaneous and subcutaneous metastases (20—≥ 100) and in patients with subcutaneous bulky disease intralesional immunotherapy can improve the disease outcome. The exact role of intralesional immunotherapy in the age of immune checkpoint blockade has still to be determined. A number of clinical trials are on the way in order to better understand synergistic actions of intralesional and systemic immunotherapy.

KEYWORDS:

• Intralesional immunotherapy
• (T-VEC)
• Allovectin-7
• IL-2
• PV-10
• electrochemotherapy
• melanoma

Article highlights

• Intralesional therapies of cutaneous and subcutaneous melanoma metastases often result in complete remissions of the injected tumors.

• Many tumors can be treated simultaneously and more than hundred tumors were reported to achieve complete remissions with intralesional therapy only.

• With some intralesional treatment approaches, innocent bystander effects have been observed with tumor regression of distant, not injected tumors.

• Tumor remissions after intralesional therapy are most times long-lasting, and local recurrences are seldom observed.

• The mechanism of action of intralesional therapy is still unknown and the role of specific anti-tumor immune responses and innate immunity are not yet clear.

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Declaration of interest

C Garbe has received honoraria from Amgen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.