Hematological and Other Cancers in People Using Clozapine: Analysis of Australian Spontaneous Reports Between 1995 and 2020.

Background: Recent observational study evidence suggests that clozapine, unlike other antipsychotics, may be associated with a small increased risk of hematological malignancy. This study described characteristics of hematological and other cancers in those taking clozapine reported to the Australian Therapeutic Goods Administration.

Methods: We analyzed public case reports for "clozapine," "Clozaril," or "Clopine" from January 1995 to December 2020 classified as "neoplasm benign, malignant and unspecified" by the Australian Therapeutic Goods Administration. Data on age, sex, dose, clozapine start and cessation dates, Medical Dictionary for Regulatory Activities reaction terms, and date of cancer were extracted.

Results: Overall, 384 spontaneous reports of cancers in people taking clozapine were analyzed. The mean age of patients was 53.9 years (SD, 11.4 years), and 224 (58.3%) were male. The most frequent cancers were hematological (n = 104 [27.1%]), lung (n = 50 [13.0%]), breast (n = 37 [9.6%]), and colorectal (n = 28 [7.3%]). The outcome was fatal for 33.9% of cancer reports. Lymphoma comprised 72.1% of all hematological cancers (mean patient age, 52.1 years; SD, 11.6 years). The median daily dose of clozapine at the time of hematological cancer report was 400 mg (interquartile range, 300-543.8 mg), and the median duration of clozapine use before hematological cancer diagnosis was 7.0 years (interquartile range, 2.8-13.2 years).

Conclusions: Lymphoma and other hematological cancers are overrepresented in spontaneous adverse event reports compared with other cancer types. Clinicians should be aware of the possible association with hematological cancers and monitor for and report any hematological cancers identified. Future studies should examine histology of lymphomas in people using clozapine and corresponding blood level of clozapine.