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Drug Safety

, Volume 42, Issue 2, pp 281–294 | Cite as

Safety and Tolerability of Immune Checkpoint Inhibitors (PD-1 and PD-L1) in Cancer

  • Iosune Baraibar
  • Ignacio Melero
  • Mariano Ponz-Sarvise
  • Eduardo CastanonEmail author
Review Article

Abstract

Immunotherapy has emerged in recent years and has revolutionized the treatment of cancer. Immune checkpoint inhibitors, including anti-cytotoxic T lymphocyte antigen-4 (CTLA-4), anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) agents, are the first of this new generation of treatments. Anti-PD-1/PD-L1 agents target immune cells by blocking the PD-1/PD-L1 pathway. This blockade leads to enhancement of the immune system and therefore restores the tumour-induced immune deficiency selectively in the tumour microenvironment. However, this shift in the balance of the immune system can also produce adverse effects that involve multiple organs. The pattern of toxicity is different from traditional chemotherapy agents or targeted therapy, and there is still little experience in recognizing and managing it. Thus, toxicity constitutes a real clinical management challenge and any new alteration should be suspected of being treatment-related. The most common toxicities occur in the skin, gastrointestinal tract, lungs, and endocrine, musculoskeletal, renal, nervous, haematologic, cardiovascular and ocular systems. Immune-mediated toxic effects are usually manageable, but toxicities may sometimes lead to treatment withdrawal, and even fulminant and fatal events can occur. Oncologists need to collaborate with internists, clinical immunologists and other specialists to understand, manage and prevent toxicity derived from immunotherapy. This review focuses on the mechanisms of toxicity of anti-PD-1/PD-L1 agents, and its diagnosis and management.

Notes

Compliance with Ethical Standards

Conflict of interest

Iosune Baraibar, Mariano Ponz-Sarvise and Eduardo Castanon have no conflicts of interest to declare that are directly relevant to the contents of this study. Ignacio Melero has received grants from Roche, BMS, Alligator and Bioncotech, as well as consulting fees from BMS, Roche, Bioncotech, Genmab, Cytomx, F-Star, Alligator and EMD.

Funding

No sources of funding were used to assist in the preparation of this study.

Ethical approval/patient consent

Not applicable.

Supplementary material

40264_2018_774_MOESM1_ESM.pdf (182 kb)
Supplementary material 1 (PDF 182 kb)

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Iosune Baraibar
    • 1
    • 2
  • Ignacio Melero
    • 1
    • 2
    • 3
    • 4
  • Mariano Ponz-Sarvise
    • 1
    • 2
    • 4
  • Eduardo Castanon
    • 1
    Email author
  1. 1.Departamento de Oncología. ClínicaUniversidad de NavarraPamplonaSpain
  2. 2.Centro de investigación médica Aplicada (CIMA)PamplonaSpain
  3. 3.Centro Virtual de la Investigación Biomédica en red en Oncología (CIBERONC)MadridSpain
  4. 4.IdiSNAPamplonaSpain

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