Study Finds Low Risk of Blood Cancer in Clozapine-Treated Patients

An inter-departmental research team from the LKS Faculty of Medicine at the University of Hong Kong (HKUMed) has conducted an innovative and pioneering study that sheds light on the safety of clozapine, a highly effective antipsychotic medication, particularly in relation to the incidence of blood cancer. This world-first analytic real-world cohort study used territory-wide electronic health records to analyze data and evaluate the association between clozapine usage and blood cancer risk. The findings from this study present crucial insights that may impact clinical practices and decision-making regarding the use of clozapine in the treatment of schizophrenia.

Clozapine is widely regarded as a last-resort treatment for treatment-resistant schizophrenia, particularly in patients who do not respond to other antipsychotic medications. Approved by the Food and Drug Administration (FDA) in the United States, clozapine is well known for its potent efficacy in managing the symptoms of schizophrenia, reducing relapse rates, and decreasing all-cause mortality. Despite its clinical benefits, clozapine has been associated with some severe side effects, including the potential to cause agranulocytosis (a potentially life-threatening reduction in white blood cells). As a result, clinicians typically implement stringent blood monitoring protocols to ensure patient safety during clozapine treatment.

However, the relationship between clozapine and blood cancer has been a subject of ongoing concern and debate. Several studies, particularly in Finland and the United States, have suggested that clozapine use could potentially elevate the risk of blood cancers, such as leukemia. These findings, though concerning, were based on relatively limited data, which made it difficult to definitively estimate the additional number of blood cancer cases linked to clozapine use and assess the clinical significance of this potential risk. As a result, clozapine’s safety profile, especially regarding blood cancer, remained uncertain.

In response to these concerns, the research team at HKUMed conducted an extensive study using electronic health records from the Hospital Authority of Hong Kong, spanning over two decades from 2001 to 2022. The team identified a cohort of approximately 10,000 patients diagnosed with schizophrenia, all of whom were treated with clozapine. The patients were followed for a median period of seven years, providing valuable longitudinal data on the potential adverse effects of the drug, including the incidence of blood cancer.

The study’s results revealed that the absolute risk of developing blood cancer in patients using clozapine was extremely low. Among the 10,000 patients who were followed over the seven-year period, only 39 individuals developed blood cancer. After adjusting for various confounding factors, the researchers estimated that there were fewer than six new cases of blood cancer per 10,000 patients who used clozapine for one year. This rate of incidence was notably low, suggesting that the association between clozapine and blood cancer is, in fact, minimal.

Furthermore, the researchers examined the relative risk of blood cancer between clozapine users and those who did not use clozapine, and found a weighted incidence rate ratio of 2.22. This means that clozapine users had a slightly higher risk of developing blood cancer compared to the general population, but the absolute risk increase was still quite low. These findings are consistent with previous case-control studies from Finland and the United States, which also suggested a possible, albeit small, increase in blood cancer risk.

However, it is essential to note that no significant association was found between clozapine and other forms of cancer in the study, further strengthening the argument that the risk of blood cancer, while present, is an isolated concern. The study’s authors suggest that this minimal risk may be mitigated by the existing blood monitoring protocols currently in place for patients taking clozapine. These protocols, which involve regular blood tests to detect any early signs of agranulocytosis or other hematological issues, are considered comprehensive and effective in ensuring patient safety.

Professor Francisco Lai Tsz-tsun, the project leader and Assistant Professor at both the Department of Pharmacology and Pharmacy and the Department of Family Medicine and Primary Care at HKUMed, emphasized that the study’s findings provide robust and reliable evidence that can help healthcare professionals make more informed decisions regarding the use of clozapine. “In response to Western studies suggesting a potential risk of blood cancer after clozapine use, this study provides reliable evidence for patients and health care professionals supporting the safety of the drug,” said Professor Lai. He went on to reassure clinicians and patients that the current blood monitoring measures in place are more than adequate to safeguard against the rare occurrence of blood cancer associated with clozapine.

Professor Lai also highlighted the strengths of the study’s design, which leveraged the extensive and longitudinal health data available in Hong Kong’s public healthcare system. The ability to link and analyze data across all public healthcare facilities in Hong Kong provided the researchers with a unique advantage in assessing real-world health outcomes. This big data approach enabled the team to produce findings that are more robust and applicable to clinical practice than many studies conducted in other countries with smaller, less comprehensive data sets.

While the study’s findings offer reassuring evidence regarding the safety of clozapine, the research team is not stopping there. They are currently exploring the long-term safety and effectiveness of other psychotropic medications, particularly their potential links to cancer and other serious side effects. By expanding the scope of their research, the team aims to further improve the safety and efficacy of medications used to treat mental illness, ultimately benefiting both patients and clinicians alike.

The implications of this study are far-reaching. It suggests that the potential risks of blood cancer associated with clozapine, while present, are unlikely to require additional restrictions or special warnings by health authorities. As the study demonstrates, clozapine’s benefits in managing treatment-resistant schizophrenia far outweigh the minimal risks when appropriate monitoring protocols are followed. This reassurance can help ensure that patients continue to receive the best possible treatment for their condition without unnecessary hesitation or concern.

Moreover, the study highlights the value of utilizing large-scale healthcare data to address pressing clinical questions. By tapping into big data, researchers can gain deeper insights into the safety and efficacy of drugs, leading to more accurate and evidence-based healthcare decisions. As such, this research exemplifies the transformative potential of data-driven studies in advancing medical science and improving patient care.

Reference: Yuqi Hu et al, Rare but elevated incidence of hematological malignancy after clozapine use in schizophrenia: A population cohort study, PLOS Medicine (2024). DOI: 10.1371/journal.pmed.1004457