Identifying and treating candidates for checkpoint inhibitor therapies in multiple myeloma and lymphoma

ABSTRACT

Introduction: One of the hallmarks of cancerogenesis is the ability of tumor cells to evade the immune system. They can achieve it by abusing inhibitory immune checkpoint pathways, which, under normal circumstances, maintain peripheral tolerance during infection. Immune checkpoint inhibitors, especially anti-PD-1/PD-L1 monoclonal antibodies, currently represent a widely discussed treatment option not only in solid oncology, but in hematology-oncology as well.

Areas covered: The manuscript is focused on clinical research concerning PD-1/PD-L1 blockade in lymphoma and multiple myeloma in order to identify the patients who would profit the most from this treatment modality. The authors reviewed articles on the topic on PubMed and relevant clinical trials on clinicaltrials.gov before October 2019.

Expert opinion: So far, nivolumab and pembrolizumab have been approved for treating patients with relapsed/refractory classical Hodgkin lymphoma and primary mediastinal B cell lymphoma. Nevertheless, monotherapy alone is not curative and a combinational approach is needed. Modern treatment strategies and combinations are comprehensively summarized in this manuscript. There is no approved immune checkpoint inhibitor for the multiple myeloma indication. Although the combination of PD-1/PD-L1 inhibitors with immunomodulatory agents initially seemed promising, unexpected immune related toxicities have stopped any further development. Novel strategies and more potent combinations in myeloma and lymphoma are further discussed in the manuscript.

KEYWORDS:

• Atezolizumab
• cemiplimab
• durvalumab
• lymphoma
• multiple myeloma
• nivolumab
• PD-1
• PD-L1
• pembrolizumab

Article highlights

• PD-1/PD-L1 inhibitors monotherapy is not effective in multiple myeloma

• Combination of anti-PD-1/PD-L1 monoclonal antibodies with immunomodulatory drugs is active but not safe due to increased immune related toxicity

• No checkpoint inhibitor is currently approved in multiple myeloma, but this treatment strategy should not be abandonded as a subset of relapsed/refractory multiple myeloma patients may benefit from this approach

• Pembrolizumab and nivolumab have been approved in relapsed/refractory classical Hodgkin lymphoma and primary mediastinal large B cell lymphoma.

• Monotherapy with immune checkpoints does not seem to have curative potential in lymphoma, the combinational approach is needed and, in our opinion, the most promising partners are brentuximab vedotin, blinatumomab and CAR-T cells

Acknowledgments

The authors would like to give thanks to Shira Timilsina Godfrey, M.D. for editing the article.

Declaration of interest

The authors have no 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 funded by: the Institutional Development Plan of University of Ostrava and The Ministry of Education, Youth and Sports [IRP03_2018‐2020]; MH CZ—DRO (FNOs/2019); the European Regional Development Fund - Project ENOCH [No. CZ.02.1.01/0.0/0.0/16_019/0000868]; the European Regional Development Fund - Project New Directions of Biomedical Research in the Ostrava Region [CZ.02.1.01/0.0/0.0/18_069/0010060].