Baseline lymphopenia as prognostic factor in patients with metastatic breast cancer treated with palbociclib

Emile, George; Penager, Sarah; Lévy, Christelle; Johnson, Alison; Allouache, Djelila; Lequesne, Justine; Hrab, Ioana; Ségura, Carine; Morel, Adeline; Gunzer, Katarina; Faveyrial, Audrey; Cherifi, François; Silva, Angélique Da

doi:10.3892/ol.2021.13143

Cited by 13 publications

(17 citation statements)

References 50 publications

(64 reference statements)

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“…Concerning patients treated with palbociclib for HR+/HER2-mBC, we previously showed that those with pretherapeutic ALC< 1.5 G/L had signi cantly shorter PFS time (6 vs. 10 months, p=0.004), shorter OS time (20 vs. 33 months, p=0.018) and more disease progression at rst imaging evaluation [31].…”

Section: Discussionmentioning

confidence: 97%

Pretreatment neutrophil to lymphocyte ratio as prognostic factor in metastatic breast cancer treated with cyclin dependent kinase 4/6 inhibitors

Rottier

SILVA

Johnson

et al. 2022

Preprint

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Background: Cyclin dependent kinase inhibitors (CdK4/6i) changed the course of hormone receptor positive (HR+) HER2negative (HER2-) metastatic breast cancer (mBC). To date, no factors have been shown to predict response to CdK4/6i. Neutrophil-to-lymphocyte ratio (NLR), an indicator of the host systemic inflammatory response, is an independent prognostic factor for survival in cancers. We conducted this study to evaluate the addition of NLR for survival assessment in mBC patients treated with first line CdK4/6i. Methods: All mBC patients treated with first line CdK4/6i between November 2015 and December 2019 were retrospectively included. We analyzed 12-month progression free survival (PFS), overall survival (OS) and response rate according to NLR in univariable and multivariable analysis.Results: A total of 126 patients treated with palbociclib (n=101), ribociclib (n=18) or abemaciclib (n=7) were included, with a median follow-up of 16 months [range: 2.9-37]. Median age was 65 years [29-86], 88% patients had good performance status (0-1). Most patients were included at the metastatic relapse stage (71%) and 20% had visceral metastases without bone lesions. High NLR (≥ 2.53) was significantly associated with worse PFS (Hazard Ratio (HR)=0.52, CI95% =[0.29-0.94]). Fourteen patients died (11.1%). Complete responses were more frequent in the low NLR group (<2.53) (14.5% vs. 3.1%, p=0.029). Conclusion: High NLR is associated with worse PFS in HR+ HER2- mBC patients treated with first line CdK4/6i. NLR is a reliable and inexpensive prognostic marker, easily accessible in routine clinical practice, which could optimize the therapeutic strategy. These results need to be confirmed in larger prospective studies.

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Section: Discussionmentioning

confidence: 97%

Pretreatment neutrophil to lymphocyte ratio as prognostic factor in metastatic breast cancer treated with cyclin dependent kinase 4/6 inhibitors

Rottier

SILVA

Johnson

et al. 2022

Preprint

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“…It is not yet known whether there is a correlation between lymphocytopenia and poor survival and an association between the specific subset of lymphocytes and inferior prognosis. Previous studies have reported that lymphopenia is an adverse prognostic factor in various solid tumors, Hodgkin's lymphoma (HL), and NHL (24)(25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

Low absolute CD4+ T cell counts in peripheral blood: an independent predictor of inferior survival in natural killer/T-cell lymphoma—a retrospective cohort study

Zeng¹,

Zhu²,

Jiang³

et al. 2022

Ann Transl Med

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Background: Lymphopenia at diagnosis is considered a negative prognostic factor for patients with extra-nodal natural killer (NK)/T-cell lymphoma (ENKTL), especially that of the absolute cluster of differentiation 4 + T cell count (ACD4C), which has previously been identified as an independent prognostic factor in other hematologic malignancies. However, there is limited data available regarding the prognostic value of peripheral blood T lymphocyte subsets in ENKTL patients. The purpose of this study was to investigate the prognostic value of lymphocyte subsets, especially the ACD4C in ENKTL as a clinical biomarker.Methods: We analyzed the clinical data of 176 patients who met the inclusion criteria in Cancer Center

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“…For the reasons above, CDK4/6 therapy associated with ET is considered the gold-standard treatment for HR+/HER2− mBC with no extensive visceral involvement. Despite the survival benefits of CDK4/6 inhibitors, resistance occurs in a large fraction of patients (approximately 15% and 30% in those administered with CDK4/6 plus anti-aromatase inhibitors or fulvestrant, respectively) [ 18 ]. Further research by Turner et al showed that a potential resistance mechanism to CDK4/6 treatment—and thus leading to tumour relapse—might involve specific mutations occurring in Rb , ERS1, and PIK3 CA genes [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have mainly focused on the local immune response within the tumour microenvironment; however, several studies have shown that the local antitumour immune response is connected to the systemic immune response [ 23 ]. Additionally, some trials have observed that unexpected T cell clones in the peripheral blood might lead to better outcomes [ 18 ]. The role of circulating immune cells in the control of tumour response to therapies has gained widespread interest over the last decade, and baseline lymphopenia has been observed as a potential prognostic factor in different types of cancer [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, some trials have observed that unexpected T cell clones in the peripheral blood might lead to better outcomes [ 18 ]. The role of circulating immune cells in the control of tumour response to therapies has gained widespread interest over the last decade, and baseline lymphopenia has been observed as a potential prognostic factor in different types of cancer [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Clinico-Immunological Effects of a Single-Agent CDK4/6 Inhibitor in Advanced HR+/HER2− Breast Cancer Based on a Window of Opportunity Study

D’Angelo

Giudici

Chapman

et al. 2022

CIMB

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Background : Cyclin-dependent kinase 4/6 inhibitors (CDK4/6 i), abemaciclib, palbociclib, and ribociclib, have been FDA-approved for the treatment of hormone receptor-positive (HR+), HER2−negative (HER2−) advanced breast cancer (aBC). This targeted therapy has revived hope in those aBC patients who did not respond to standard therapies. Interestingly, when administered as a single agent, CDK4/6 modulated several peripheral blood cells after a short-course treatment of 28 days. However, the impact of these immune effects has yet to be thoroughly investigated. Methods : We administered abemaciclib, palbociclib, and ribociclib monotherapy to 23 patients with HR+/HER2− metastatic breast cancer. The aim is to investigate the impact of on-treatment modifications on peripheral blood cells and their composite scores in patients after a 28-day course of CDK4/6 i alone. Results : In the current study, we observed a significant decrease in neutrophils ( p -value < 0.001) for patients treated with abemaciclib, palbociclib, and ribociclib. An overall decrease of T regs was observed and potentially linked to palbociclib treatment. The neutrophile to lymphocyte (N/L) ratio was also decreased overall and potentially linked to abemaciclib and palbociclib treatment. Platelets were decreased in patients administered with abemaciclib. Notably, the radiometabolic response was available only for those patients treated with ribociclib and abemaciclib, and only those lesions treated with ribociclib reached statistical relevance. Conclusions : Our study strongly supports the notion that CDK4/6 inhibitors induce tumour immune modulation. N/L ratio and platelet levels decreased due to treatment. Future studies should test whether patients would benefit from immunomodulators in association with CDK4/6 agents in a larger clinical trial. Moreover, the CDK4/6-induced immune modulation could also be considered a potential predictive clinical factor in HR+/HER2− advanced breast cancer.

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Baseline lymphopenia as prognostic factor in patients with metastatic breast cancer treated with palbociclib

Cited by 13 publications

References 50 publications

Pretreatment neutrophil to lymphocyte ratio as prognostic factor in metastatic breast cancer treated with cyclin dependent kinase 4/6 inhibitors

Pretreatment neutrophil to lymphocyte ratio as prognostic factor in metastatic breast cancer treated with cyclin dependent kinase 4/6 inhibitors

Low absolute CD4+ T cell counts in peripheral blood: an independent predictor of inferior survival in natural killer/T-cell lymphoma—a retrospective cohort study

Clinico-Immunological Effects of a Single-Agent CDK4/6 Inhibitor in Advanced HR+/HER2− Breast Cancer Based on a Window of Opportunity Study

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