Anaemia during targeted anticancer therapy: pathogenesis, clinical features and modern correction approaches

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Abstract

Aim. To systematise current data on the mechanisms of anaemia development with major targeted anticancer drug classes, evaluate its impact on quality of life and summarise modern correction approaches.

Materials and methods. A narrative literature review was performed searching PubMed, eLIBRARY and Cochrane Library with no date restrictions. Randomised clinical trials, meta-analyses, pharmacovigilance studies and current clinical guidelines (ESMO, ASCO/ASH) were analysed for the following drug classes: antibody–drug conjugates (ADCs), PARP inhibitors (PARPi), tyrosine kinase inhibitors and immune checkpoint inhibitors.

Results. Anaemia occurs in 30–80 % of cancer patients and represents an independent prognostic factor for worse overall survival. ADC haematological toxicity is off-target and payload-driven: conjugates based on monomethylauristatin E carry the highest rates of severe anaemia. PARPi cause anaemia as a class effect via disruption of PARP-2-dependent erythroid differentiation. Tyrosine kinase inhibitors exert haematotoxicity through molecularly specific pathways, including disruption of erythrocyte membrane integrity. Immune checkpoint inhibitors are associated with immune-mediated haemolytic anaemia and aplastic syndrome. Among correction approaches, intravenous iron preparations and sucrosomial iron overcome the hepcidin-mediated functional block unachievable with classical oral salts. Erythropoiesis-stimulating agents are indicated under strict conditions given thromboembolic risk and potential immunosuppressive effects on the tumour microenvironment.

Conclusion. Pathogenetically sound correction of anaemia during targeted therapy requires a differentiated approach accounting for the development mechanism, type of iron deficiency and targeted agent class. Blood count monitoring no later than 2 weeks from the first cycle start is mandatory for patients receiving ADCs, PARPi and immune checkpoint inhibitors.

About the authors

Rashida V. Orlova

Saint Petersburg State University; Saint Petersburg City Clinical Oncology Dispensary

Email: dr.s.kutukova@gmail.com
ORCID iD: 0000-0003-4447-9458
Russian Federation, 8a 21st line of Vasilievsky Island, Saint Petersburg 199106; 56 Veteranov Prospekt, Saint Petersburg 198255

Svetlana I. Kutukova

Acad. I.P. Pavlov First Saint Petersburg State Medical University

Author for correspondence.
Email: dr.s.kutukova@gmail.com
ORCID iD: 0000-0003-2221-4088
Russian Federation, 6–8 Lev Tolstoy St., Saint Petersburg 197022

Natalia P. Belyak

Saint Petersburg State University; Saint Petersburg City Clinical Oncology Dispensary

Email: dr.s.kutukova@gmail.com
ORCID iD: 0000-0003-0402-6067
Russian Federation, 8a 21st line of Vasilievsky Island, Saint Petersburg 199106; 56 Veteranov Prospekt, Saint Petersburg 198255

Aleksandra V. Androsova

Saint Petersburg State University; Saint Petersburg City Clinical Oncology Dispensary

Email: dr.s.kutukova@gmail.com
ORCID iD: 0000-0001-7111-1507
Russian Federation, 8a 21st line of Vasilievsky Island, Saint Petersburg 199106; 56 Veteranov Prospekt, Saint Petersburg 198255

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