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Haematologic Toxicity Not Increased with Immunochemotherapy Combinations Over Chemotherapy Treatment for Solid Tumours

Immunochemotherapy combinations have demonstrated improved efficacy over sole chemotherapy in diverse solid tumours
09 Dec 2020
Cancer Immunology and Immunotherapy

No significant increase in all-grade haematologic toxicity was found with the addition of an anti-PD1/PD-L1-based or anti-CTLA4-based therapy to chemotherapy as compared to chemotherapy alone in patients with solid tumours, according to findings presented at the ESMO Immuno-Oncology Virtual Congress 2020, held from 9 to 12 December 2020.

Lead poster author Daniel Eiger of the Clinical Trials Support Unit, Institut Jules Bordet in Brussels, Belgium noted that combination of immunotherapy and chemotherapy has become a standard treatment option in several settings, but whether there is an additive toxicity effect had not been sufficiently investigated. This question prompted an evaluation of treatment-induced myelotoxicity and immune-mediated cytopenias due to the addition of an immune checkpoint inhibitor (ICI) to chemotherapy.

This meta-analysis initiated a systematic review of the MEDLINE and Cochrane databases as well as conference proceedings, according to a manual selection of studies presented at major congresses, that occurred up to 5 June 2020. The review was restricted to English language publications and included randomised clinical studies comparing immunotherapy/chemotherapy combinations to chemotherapy in patients with solid tumours.

The main endpoints of the analysis included all-grade anaemia, neutropenia, febrile neutropenia (FN), and thrombocytopenia. The same cytopenias grouped by grades 1 to 2, 3 to 4, and 5 served as the other endpoints. Subgroup analyses were performed according to the class of ICI and a sensitivity analysis that excluded trials with a different number of cycles of chemotherapy between arms was done. Random effects models were used in pooled odds ratio (pOR) and confidence interval (CI) calculations.

The incidence of all-grade cytopenia was not increased with the addition of an immunotherapy to chemotherapy

The investigators identified 19 publications; of these, 14 assessed anti-PD1/PD-L1-based immunochemotherapy and 5 evaluated an anti-CTLA4-based combination, with a total of 5254 patients in the immunotherapy/chemotherapy arm and 4316 in the chemotherapy arm.

Comparison of the immunotherapy/chemotherapy and chemotherapy arms provided pooled incidences of all-grade cytopenias. The specific incidences were: Anaemia 42% versus 38%, neutropenia 33% versus 30%, FN 7% versus 5%, and thrombocytopenia 20% versus 17%, respectively.

No significant increase in the odds of all-grade adverse events (AEs) was found for immunotherapy/chemotherapy compared to chemotherapy in any of the cytopenias evaluated: Anaemia (pOR 1.04; 95% CI 0.90-1.21; p = 0.58), neutropenia (pOR 1.01; 95% CI 0.87-1.16; p = 0.94), FN (pOR 1.24; 95% CI 0.97-1.58; p = 0.09), and thrombocytopenia (pOR 1.14; 95% CI 1.00-1.30; p = 0.06). No significant increase in the odds of G1-2, G3-4, and G5 adverse events (AEs) were found as well.

In subgroup analysis according to major class of ICI (anti-PD(L)1-based immunotherapy/chemotherapy and anti-CTLA-4-based immunotherapy/chemotherapy), only a small albeit statistically significant increment in the odds of all grade thrombocytopenia was found with an anti-PD1/PD-L1-based immunotherapy/chemotherapy compared to chemotherapy (pOR 1.18; 95% CI 1.02-1.36; p = 0.03).

Haematologic-Toxicity-Not-Increased-with-Immunochemotherapy-Combinations-Over-Chemotherapy-Treatment-for-Solid-Tumours

Pooled incidences and pooled Odds Ratio (pOR) with 95% confidence intervals (95% CI) in the immunotherapy/chemotherapy vs. chemotherapy alone groups and subgroups, according to major immune checkpoint inhibitor classes.

© Daniel Eiger.

The sensitivity analysis provided similar results.

Conclusions

The authors of the poster wrote that, apart from a small increase in the odds of all grade thrombocytopenia with anti-PD1/PD-L1-based immunochemotherapy, the combination of an immunotherapy plus chemotherapy appears to be as safe as chemotherapy in terms of haematological toxicities.

No external funding was disclosed.

Reference

44P – Eiger D, Agostinetto E, Caparica R, et al. The hematologic toxicities of chemo-immunotherapy compared to chemotherapy alone: A systematic review and meta-analysis. ESMO Immuno-Oncology Virtual Congress 2020 (9-12 December).

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