Immune checkpoint inhibitors for the treatment of myeloma: novel investigational options

ABSTRACT

Introduction

Multiple myeloma (MM) is still considered incurable and the outcome of patients with triple-class refractory remains very poor. Immunotherapy is considered as a standard of care for the treatment of MM. Among immunotherapeutic approaches, the PD-1/PD-L1 axis is an attractive target because PD-L1 is highly expressed in most myeloma plasma cells. While many types of cancer benefit from checkpoint inhibitor treatment, their relevance in multiple myeloma needs to be defined.

Areas covered

The authors evaluate the published data regarding the mechanism of action, safety profile, and clinical efficacy of the immune checkpoint inhibitors (ICI) for the treatment of multiple myeloma.

Expert opinion

The use of ICI monotherapy does not offer any clinical benefit in myeloma patients. In combination with immunomodulatory drugs (IMID), ICI failed to demonstrate clinical benefit and were associated with increased toxicity. Given the toxicities of these treatments, predictive markers would be useful to select patients who would benefit most. Clinical studies are necessary to evaluate the safety and efficacy of checkpoint inhibitors in combination with other standards of care such as proteasome inhibitors and monoclonal antibodies. The combination of anti-PD-1 with T-cell engager (TCE) or CAR-T cells seems theoretically attractive and should be explored in clinical trials.

KEYWORDS:

• Immune checkpoints
• PD-1
• PD-L1
• multiple myeloma
• nivolumab
• pembrolizumab

Article highlights

• PD-L1 is highly expressed in most myeloma plasma cells and is associated with aggressive characteristics of multiple myeloma (MM)

• Used as single agent in MM, anti PD-1 showed favorable safety profile but did not demonstrate any clinical benefit.

• Phase III studies combining anti-PD-1 and immunomodulatory drugs (IMID) have failed to demonstrate any clinical benefit and have presented worrying and incompletely understood toxicities, leading to their suspension by the FDA.

• Other combinations are promising, in particular, with proteasome inhibitors or monoclonal antibodies. Studies are ongoing to evaluate their safety and efficacy.

• Given the potential toxicities of these treatments and their inconsistent efficacy, the development of biomarkers to predict response is anticipated.

• Immune checkpoints appear to play a key role in the exhaustion of anti-B cell maturation antigen (BCMA) CAR-T cells in MM.

Declaration of interest

C Touzeau and P Moreau are advisory board members for, and received honoraria from BMS, Celgene, Amgen, Janssen, and Merck. 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded