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

Expert Rev Hematol. 2020 Apr;13(4):375-392. doi: 10.1080/17474086.2020.1733405. Epub 2020 Mar 2.

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; PD-1; PD-L1; cemiplimab; durvalumab; lymphoma; multiple myeloma; nivolumab; pembrolizumab.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Video-Audio Media

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents, Immunological / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / immunology
  • Hodgkin Disease / drug therapy*
  • Hodgkin Disease / immunology
  • Hodgkin Disease / pathology
  • Humans
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / pathology
  • Mediastinal Neoplasms / drug therapy*
  • Mediastinal Neoplasms / immunology
  • Mediastinal Neoplasms / pathology
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / immunology
  • Multiple Myeloma / pathology
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / immunology
  • Nivolumab / therapeutic use*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • CD274 protein, human
  • Neoplasm Proteins
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab
  • pembrolizumab