Excess of blood eosinophils prior to therapy correlates with worse prognosis in mesothelioma

Our plain-English summary of Excess of blood eosinophils prior to therapy correlates with worse prognosis in mesothelioma, by M. Willems, A. Scherpereel, E. Wasielewski, et al (Frontiers in Immunology, 2023).

The study

• Authors: M. Willems, A. Scherpereel, E. Wasielewski, J. Raskin, H. Brossel, A. Fontaine, M. Grégoire, L. Halkin, M. Jamakhani, V. Heinen, R. Louis, B. Duysinx, M. Hamaidia, L. Willems
• Journal: Frontiers in Immunology
• Published: 2023;14:1148798
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Only a fraction of patients with malignant pleural mesothelioma (MPM) will respond to chemo- or immunotherapy. For the majority, the condition will irremediably relapse after 13 to 18 months. In this study, we hypothesized that patients' outcome could be correlated to their immune cell profile. Focus was given to peripheral blood eosinophils that, paradoxically, can both promote or inhibit tumor growth depending on the cancer type.

Methods: The characteristics of 242 patients with histologically proven MPM were retrospectively collected in three centers. Characteristics included overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR). The mean absolute eosinophil counts (AEC) were determined by averaging AEC data sets of the last month preceding the administration of chemo- or immunotherapy.

Results: An optimal cutoff of 220 eosinophils/µL of blood segregated the cohort into two groups with significantly different median OS after chemotherapy (14 and 29 months above and below the threshold, p = 0.0001). The corresponding two-year OS rates were 28% and 55% in the AEC ≥ 220/µL and AEC < 220/µL groups, respectively. Based on shorter median PFS (8 vs 17 months, p < 0.0001) and reduced DCR (55.9% vs 35.2% at 6 months), the response to standard chemotherapy was significantly affected in the AEC ≥ 220/µL subset. Similar conclusions were also drawn from data sets of patients receiving immune checkpoint-based immunotherapy.

Conclusion: In conclusion, baseline AEC ≥ 220/µL preceding therapy is associated with worse outcome and quicker relapse in MPM.

Copyright © 2023 Willems, Scherpereel, Wasielewski, Raskin, Brossel, Fontaine, Grégoire, Halkin, Jamakhani, Heinen, Louis, Duysinx, Hamaidia and Willems.

In plain English

This retrospective study reviewed records of 242 malignant pleural mesothelioma patients treated between 2009 and 2021 at three hospitals in Belgium and France. The authors averaged each patient's blood eosinophil count (eosinophils are a type of white blood cell) over the month before chemotherapy or immunotherapy, and chose a cutoff of 220 per microlitre. Of 230 patients given first-line chemotherapy, 61 were at or above the cutoff and 169 were below it. Median overall survival was 14 months in the higher-count group and 29 months in the lower-count group (hazard ratio 2.063, 95% CI 1.420 to 2.998). Median progression-free survival was 8 versus 17 months. Objective response rates (complete or partial tumor shrinkage) were similar, but the higher-count group had lower 6-month disease control (35.2% versus 55.9%) and more progressive disease (33.3% versus 17.2%). Immunotherapy patients showed a similar pattern. At one hospital, Liege, the difference was not statistically significant. Asbestos exposure was confirmed in 28.4% of the lower-count group and 34.4% of the higher-count group. The authors concluded that the cutoff identified groups with distinct outcomes. They noted that a causal link remains unproven and called for prospective studies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective observational study of hospital records from three centers
• Who was studied: 242 patients with malignant pleural mesothelioma treated at the university hospitals of Liege and Antwerp (Belgium) and Lille (France) between January 2009 and December 2021. 230 received first-line chemotherapy and 12 received immune checkpoint inhibitors as first-line therapy. Patients with autoimmune disease, immunodeficiency, asthma or active parasitic infection were excluded.
• Exposure: The factor studied was the absolute blood eosinophil count, averaged over the month before therapy and split at 220 per microlitre. Treatments were cisplatin or carboplatin plus pemetrexed chemotherapy, or nivolumab plus ipilimumab immunotherapy. Asbestos exposure was recorded only partially: it was confirmed in 28.4% of the lower-count group and 34.4% of the higher-count group.
• Main results:
  • The 220 per microlitre cutoff split the 230 chemotherapy patients into 169 below and 61 at or above the cutoff.
  • Median overall survival after chemotherapy was 14 months for patients at or above 220 per microlitre and 29 months for those below (p = 0.0001; hazard ratio 2.063, 95% CI 1.420 to 2.998).
  • Two-year overall survival was 28% (17.4 to 39.0) in the higher-count group and 55% (46.6 to 62.6) in the lower-count group. At one year the figures were 58% and 79%.
  • Median progression-free survival after chemotherapy was 8 months in the higher-count group and 17 months in the lower-count group (p less than 0.0001; hazard ratio 2.589, 1.606 to 4.173).
  • Objective response rates (complete plus partial response) were similar in the lower-count and higher-count groups: 15.9% vs 20.4% at 3 months, and 9.0% vs 9.3% at 6 months.
  • The disease control rate (complete or partial response, or stable disease) was better in the lower-count group. At 6 months it was 55.9% (81 of 145) below the cutoff and 35.2% (19 of 54) at or above it, per Table 2.
  • Progressive disease was more common in the higher-count group (33.3%) than in the lower-count group (17.2%).
  • In patients receiving immunotherapy, those with counts at or above 220 per microlitre before treatment had shorter overall survival (p = 0.0022) and more progressive disease (42.9% vs 18.9%).
  • At the Liege hospital, there was no statistically significant survival difference between the groups (17 vs 15 months, p = 0.4610).
  • Counts of other white blood cells (lymphocytes, monocytes, neutrophils) were similar in the two groups.
• The authors' conclusion: The authors concluded that a blood eosinophil count threshold of 220 per microlitre measured before therapy identified groups of mesothelioma patients with distinct outcomes. They said this supports further prospective analysis and possibly interventional trials.
• Limitations the authors state:
  • Because the study was retrospective, information on asbestos exposure, performance status, smoking, diabetes and BAP-1 was only partial.
  • Clinical staging was not available for most patients.
  • The lack of a difference at the Liege hospital may indicate a center bias.
  • Successive CT evaluations and clearly distinguishable tumor margins were often missing.
  • The number of first-line immunotherapy patients was limited.
  • A causal link between eosinophil count and survival has not been demonstrated.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Prognosis, Mesothelioma, Pleural Mesothelioma, Immunotherapy, Overall Survival, Progression-Free Survival, Chemotherapy.

Related studies

• The impact of Charcot-Leyden Crystal protein on mesothelioma chemotherapy: targeting eosinophils for enhanced chemosensitivity — M. Willems, M. Hamaidia, et al. (2024)
• CD70 expression correlates with a worse prognosis in malignant pleural mesothelioma patients via immune evasion and enhanced invasiveness — S. Inaguma, J. Lasota, et al. (2020)
• High blood neutrophil-to-lymphocyte ratio is an indicator of poor prognosis in malignant mesothelioma patients undergoing systemic therapy — S.C. Kao, N. Pavlakis, et al. (2010)
• Preoperative neutrophil-to-lymphocyte ratio correlates with PD-L1 expression in immune cells of patients with malignant pleural mesothelioma and predicts prognosis — R. Okita, N. Kawamoto, et al. (2023)
• Tumoral CD10 expression correlates with aggressive histology and prognosis in patients with malignant pleural mesothelioma — K. Kadota, J. Villena-Vargas, et al. (2015)
• The Value of COX-2, NF-κB, and Blood Routine Indexes in the Prognosis of Malignant Peritoneal Mesothelioma — W. Yin, G. Zheng, et al. (2019)

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