An update on the safety of nivolumab for the treatment of advanced melanoma

ABSTRACT

Introduction: Due to its unique mechanism of action as an immune checkpoint inhibitor, nivolumab has high antitumor activity, but at the same time this mechanism is responsible for immune-related adverse events that may limit patients’ safety and therapy continuation.

Areas covered: Long-term safety of nivolumab including 5-year follow-up, safety of nivolumab treatment after ipilimumab therapy, safety of nivolumab in challenging subgroups (elderly, patients with brain metastases, patients with autoimmune disorders), safety of nivolumab in with rare melanoma subtypes (including mucosal melanoma), as well as specificity of AEs reported for nivolumab treatment in melanoma patients in comparison to other cancer types and other immunotherapy molecules, and impact of AEs on response rates and PFS on nivolumab treatment are discussed.

Expert opinion: Search for biomarkers that would help us to identify patient populations that may suffer from severe nivolumab toxicity could help in selecting patients that should not be treated with this type of therapy. Novel combinations and immunotherapy drugs including use of NKTR-214 (IL-2 pathway), lymphocyte-activation gene 3 (LAG-3), local injections of talimogene laherparepvec (T-VEC), or systemic use of T-cell receptors agonists such as OX40, CD137, ICOS-1, could provide regimens with limited toxicity and higher activity.

KEYWORDS:

• Nivolumab
• melanoma
• adverse event
• immunotherapy
• toxicity

Drug summary box

Drug name: Nivolumab

Phase: 3

Indication: Melanoma – stage III and IV unresectable/metastatic as well as adjuvant after complete resection

Mechanism of action: PD-1 receptor binding

Route of administration: intravenous

Chemical structure: C6362H9862N1712O1995S42

Pivotal trials: CheckMate 066, CheckMate 067

Declaration of interest

AM Czarnecka has received honoraria for lectures from BMS and MSD. P Rutkowski has received honoraria for lectures and advisory boards from BMS, MSD, Novartis, Roche, Pierre Fabre, Amgen, Eli Lilly, Blueprint Medicines and Pfizer. 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 apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they are an employee of Immuneering Corp. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.