Haematological toxicities with immunotherapy in patients with cancer

a systematic review and meta-analysis

Fausto Petrelli, Raffaele Ardito, Karen Borgonovo, Veronica Lonati, Mary Cabiddu, Mara Ghilardi, Sandro Barni

Research output: Contribution to journalReview article

4 Citations (Scopus)

Abstract

Introduction: Programmed cell death-1 or ligand 1 (PD-(L)1) inhibitors are associated with immune-related adverse events. Conversely, little is known about the incidence of haematological toxicities across published trials. We have performed a systematic review and meta-analysis to evaluate the incidence of immunotherapy-related anaemia, neutropenia and thrombocytopenia among different tumour types, trials phases and anti-PD-(L)1 agents. Material and methods: A PubMed, Embase and Cochrane library search on 23rd December 2017 and a review of references from relevant articles were done. Studies regarding haematological diseases were excluded. The pooled incidence rates weighted for the individual sample sizes were calculated according to fixed or random effect models. Incidence of all-grade and grade (G) III or higher anaemia were the primary end-points. Neutropenia, febrile neutropenia and thrombocytopenia were secondary end-points. Results: Forty-seven studies of PD-(L)1 inhibitors for a total of 9324 evaluable patients were included in the meta-analysis. The overall incidence of anaemia during PD-(L)1 inhibitor was 9.8% (95% confidence interval [CI], 6–13.6%) for all-grade and 5% (95% CI, 3.3–6.7%) for G3-5 anaemia. The incidence was higher in diseases different from genitourinary, lung and melanoma, with avelumab and in phase II studies. In randomised trials, relative risk of all-grade anaemia for patients receiving anti-PD-(L)1 agents compared with control arms was 0.25 (95% CI, 0.16–0.39; p < 0.001). Incidence of all grades and G3-5 neutropenia and thrombocytopenia were 0.94%, 1.07%, 2.8% and 1.8%, respectively. Febrile neutropenia was 0.45%. Conclusions: The incidence of PD-(L)1 inhibitor-related anaemia was not negligible. Severe neutropenia, thrombocytopenia and febrile neutropenia were rare. These findings are useful for clinicians and suggest that blood cell count should be checked before every cycle and support should be given when severe toxicity appears.

Original languageEnglish
Pages (from-to)7-16
Number of pages10
JournalEuropean Journal of Cancer
Volume103
DOIs
Publication statusPublished - Nov 1 2018

Fingerprint

Immunotherapy
Meta-Analysis
Anemia
Incidence
Neutropenia
Thrombocytopenia
Febrile Neutropenia
Neoplasms
Confidence Intervals
CD274 Antigen
Blood Cell Count
Hematologic Diseases
PubMed
Sample Size
Libraries
Melanoma
Lung

Keywords

  • Anaemia
  • Anti-PD-(L)1
  • Cancer
  • Meta-analysis
  • Neutropenia
  • Thrombocytopenia
  • Toxicity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Haematological toxicities with immunotherapy in patients with cancer : a systematic review and meta-analysis. / Petrelli, Fausto; Ardito, Raffaele; Borgonovo, Karen; Lonati, Veronica; Cabiddu, Mary; Ghilardi, Mara; Barni, Sandro.

In: European Journal of Cancer, Vol. 103, 01.11.2018, p. 7-16.

Research output: Contribution to journalReview article

Petrelli, Fausto ; Ardito, Raffaele ; Borgonovo, Karen ; Lonati, Veronica ; Cabiddu, Mary ; Ghilardi, Mara ; Barni, Sandro. / Haematological toxicities with immunotherapy in patients with cancer : a systematic review and meta-analysis. In: European Journal of Cancer. 2018 ; Vol. 103. pp. 7-16.
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abstract = "Introduction: Programmed cell death-1 or ligand 1 (PD-(L)1) inhibitors are associated with immune-related adverse events. Conversely, little is known about the incidence of haematological toxicities across published trials. We have performed a systematic review and meta-analysis to evaluate the incidence of immunotherapy-related anaemia, neutropenia and thrombocytopenia among different tumour types, trials phases and anti-PD-(L)1 agents. Material and methods: A PubMed, Embase and Cochrane library search on 23rd December 2017 and a review of references from relevant articles were done. Studies regarding haematological diseases were excluded. The pooled incidence rates weighted for the individual sample sizes were calculated according to fixed or random effect models. Incidence of all-grade and grade (G) III or higher anaemia were the primary end-points. Neutropenia, febrile neutropenia and thrombocytopenia were secondary end-points. Results: Forty-seven studies of PD-(L)1 inhibitors for a total of 9324 evaluable patients were included in the meta-analysis. The overall incidence of anaemia during PD-(L)1 inhibitor was 9.8{\%} (95{\%} confidence interval [CI], 6–13.6{\%}) for all-grade and 5{\%} (95{\%} CI, 3.3–6.7{\%}) for G3-5 anaemia. The incidence was higher in diseases different from genitourinary, lung and melanoma, with avelumab and in phase II studies. In randomised trials, relative risk of all-grade anaemia for patients receiving anti-PD-(L)1 agents compared with control arms was 0.25 (95{\%} CI, 0.16–0.39; p < 0.001). Incidence of all grades and G3-5 neutropenia and thrombocytopenia were 0.94{\%}, 1.07{\%}, 2.8{\%} and 1.8{\%}, respectively. Febrile neutropenia was 0.45{\%}. Conclusions: The incidence of PD-(L)1 inhibitor-related anaemia was not negligible. Severe neutropenia, thrombocytopenia and febrile neutropenia were rare. These findings are useful for clinicians and suggest that blood cell count should be checked before every cycle and support should be given when severe toxicity appears.",
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T2 - a systematic review and meta-analysis

AU - Petrelli, Fausto

AU - Ardito, Raffaele

AU - Borgonovo, Karen

AU - Lonati, Veronica

AU - Cabiddu, Mary

AU - Ghilardi, Mara

AU - Barni, Sandro

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Introduction: Programmed cell death-1 or ligand 1 (PD-(L)1) inhibitors are associated with immune-related adverse events. Conversely, little is known about the incidence of haematological toxicities across published trials. We have performed a systematic review and meta-analysis to evaluate the incidence of immunotherapy-related anaemia, neutropenia and thrombocytopenia among different tumour types, trials phases and anti-PD-(L)1 agents. Material and methods: A PubMed, Embase and Cochrane library search on 23rd December 2017 and a review of references from relevant articles were done. Studies regarding haematological diseases were excluded. The pooled incidence rates weighted for the individual sample sizes were calculated according to fixed or random effect models. Incidence of all-grade and grade (G) III or higher anaemia were the primary end-points. Neutropenia, febrile neutropenia and thrombocytopenia were secondary end-points. Results: Forty-seven studies of PD-(L)1 inhibitors for a total of 9324 evaluable patients were included in the meta-analysis. The overall incidence of anaemia during PD-(L)1 inhibitor was 9.8% (95% confidence interval [CI], 6–13.6%) for all-grade and 5% (95% CI, 3.3–6.7%) for G3-5 anaemia. The incidence was higher in diseases different from genitourinary, lung and melanoma, with avelumab and in phase II studies. In randomised trials, relative risk of all-grade anaemia for patients receiving anti-PD-(L)1 agents compared with control arms was 0.25 (95% CI, 0.16–0.39; p < 0.001). Incidence of all grades and G3-5 neutropenia and thrombocytopenia were 0.94%, 1.07%, 2.8% and 1.8%, respectively. Febrile neutropenia was 0.45%. Conclusions: The incidence of PD-(L)1 inhibitor-related anaemia was not negligible. Severe neutropenia, thrombocytopenia and febrile neutropenia were rare. These findings are useful for clinicians and suggest that blood cell count should be checked before every cycle and support should be given when severe toxicity appears.

AB - Introduction: Programmed cell death-1 or ligand 1 (PD-(L)1) inhibitors are associated with immune-related adverse events. Conversely, little is known about the incidence of haematological toxicities across published trials. We have performed a systematic review and meta-analysis to evaluate the incidence of immunotherapy-related anaemia, neutropenia and thrombocytopenia among different tumour types, trials phases and anti-PD-(L)1 agents. Material and methods: A PubMed, Embase and Cochrane library search on 23rd December 2017 and a review of references from relevant articles were done. Studies regarding haematological diseases were excluded. The pooled incidence rates weighted for the individual sample sizes were calculated according to fixed or random effect models. Incidence of all-grade and grade (G) III or higher anaemia were the primary end-points. Neutropenia, febrile neutropenia and thrombocytopenia were secondary end-points. Results: Forty-seven studies of PD-(L)1 inhibitors for a total of 9324 evaluable patients were included in the meta-analysis. The overall incidence of anaemia during PD-(L)1 inhibitor was 9.8% (95% confidence interval [CI], 6–13.6%) for all-grade and 5% (95% CI, 3.3–6.7%) for G3-5 anaemia. The incidence was higher in diseases different from genitourinary, lung and melanoma, with avelumab and in phase II studies. In randomised trials, relative risk of all-grade anaemia for patients receiving anti-PD-(L)1 agents compared with control arms was 0.25 (95% CI, 0.16–0.39; p < 0.001). Incidence of all grades and G3-5 neutropenia and thrombocytopenia were 0.94%, 1.07%, 2.8% and 1.8%, respectively. Febrile neutropenia was 0.45%. Conclusions: The incidence of PD-(L)1 inhibitor-related anaemia was not negligible. Severe neutropenia, thrombocytopenia and febrile neutropenia were rare. These findings are useful for clinicians and suggest that blood cell count should be checked before every cycle and support should be given when severe toxicity appears.

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KW - Anti-PD-(L)1

KW - Cancer

KW - Meta-analysis

KW - Neutropenia

KW - Thrombocytopenia

KW - Toxicity

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