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Anaplastic Lymphoma Kinase Inhibitor-Induced Neutropenia: A Systematic Review
Fabien Moinard-Butot1, Simon Nannini1, Cathie Fischbach1
1Department of Medical Oncology, Institut de Cancérologie Strasbourg Europe, 17 Rue Albert Calmette, 67033 Strasbourg, France.
Abstract:
Lung cancers with ALK rearrangement represent less than 5% of all lung cancers. ALK inhibitors are currently used to treat first-line metastatic non-small cell lung cancer with ALK rearrangement. Compared to chemotherapy, ALK inhibitors have improved progression-free survival, overall survival, and quality of life for patients. The results of several phase 3 studies with a follow-up of over 6 years suggest that the life expectancy of these patients treated with targeted therapies is significantly higher than 5 years and could approach 10 years. Nevertheless, these treatments induce haematological toxicities, including neutropenia. Few data are available on neutropenia induced by ALK inhibitors and on the pathophysiological mechanism and therapeutic adaptations necessary to continue the treatment. Given the high efficacy of these treatments, managing side effects to avoid treatment interruptions is essential. Here, we have reviewed the data from published clinical studies and case reports to provide an overview of neutropenia induced by ALK inhibitors.
Insights
Anaplastic lymphoma kinase (ALK) inhibitors significantly improve survival for patients with ALK-rearranged lung cancer. This review details neutropenia, a side effect of ALK inhibitors, and its management to ensure treatment continuity.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Anaplastic lymphoma kinase (ALK) rearrangements occur in less than 5% of non-small cell lung cancer (NSCLC) cases.
- ALK inhibitors are a standard first-line treatment for metastatic ALK-rearranged NSCLC, demonstrating superior efficacy over chemotherapy.
- Long-term follow-up suggests significantly improved life expectancy, potentially approaching 10 years, for patients on ALK inhibitors.
Purpose of the Study:
- To review available data on neutropenia induced by ALK inhibitors in NSCLC patients.
- To provide an overview of the pathophysiological mechanisms and necessary therapeutic adaptations for managing ALK inhibitor-induced neutropenia.
- To emphasize the importance of managing side effects for uninterrupted treatment.
Main Methods:
- Systematic review of published clinical studies.
- Analysis of case reports concerning ALK inhibitor-induced neutropenia.
- Literature search for data on neutropenia, its mechanisms, and management strategies.
Main Results:
- ALK inhibitors significantly improve progression-free survival, overall survival, and quality of life compared to chemotherapy.
- Neutropenia is a notable hematological toxicity associated with ALK inhibitor therapy.
- Limited data currently exist regarding the specific mechanisms and management of ALK inhibitor-induced neutropenia.
Conclusions:
- Despite inducing neutropenia, ALK inhibitors offer substantial survival benefits for patients with ALK-rearranged NSCLC.
- Effective management of neutropenia is crucial to prevent treatment interruptions and maximize therapeutic benefits.
- Further research is needed to elucidate the mechanisms of ALK inhibitor-induced neutropenia and establish optimal management guidelines.
