Risk factors
Key risk factors that may to be linked to CLL-related mortality and disability include high body mass index, occupational exposure to benzene and formaldehyde, and smoking, which was the strongest risk factor, the authors reported.
Obesity has previously been linked with an increased risk of lymphohematopoietic cancers in general and with poorer responses to treatment and reduced progression-free survival in CLL, in particular.
While the database otherwise provided only limited insights into potential CLL risk factors, “among the factors [the database] provided, the risk of benzene and formaldehyde exposure should be paid attention to,” Dr. Wang said in an interview.
“Different from other risk factors, emerging evidence has clearly pointed out the close relationship between benzene and formaldehyde exposure and hematological malignancies,” he explained. “With globalization, a large number of factories moved to less developed regions. The problem of occupational toxic exposure needs to be addressed.”
In general, the trends in the current study are consistent with previous research showing that, while there was a significant global decrease in leukemia incidence between 1990 and 2017, the incidence rates of CLL as well as acute myeloid leukemia (AML) significantly increased in most countries during that period.
“The age-standardized incidence rate of AML has steadily increased over the past 30 years, but not as rapidly as CLL,” Dr. Wang said.
He added that an encouraging sign is the “significant decline” in the age-standardized rate of chronic myeloid leukemia seen with the advent of tyrosine kinase inhibitors (TKIs).
“Perhaps for CLL, the emergence of epoch-making therapies like TKIs will also contribute to the reduction of disease burden [with that disease],” he said.
Surveillance bias?
The authors note a key caveat that the lower rates observed in low-income regions could be related to underreporting and lower screening of cancers in those regions. However, commenting on the study, Robert Peter Gale, MD, PhD, suggested that, conversely, the trends may represent a surveillance bias, reflecting an increased detection of CLL.
In fact, “it is most unlikely the incidence of CLL is really increasing,” Dr. Gale, visiting professor of hematology at the Hematology Research Centre, department of immunology and inflammation, Imperial College London, said in an interview.
“More than one-half of people with CLL have no signs or symptoms, and the diagnosis is made when they have a blood test done for unrelated reasons,” such as in the process of qualifying for life or medical insurance or for a new job, he explained. “The more testing you do, the more cases you will detect.”
Dr. Gale pointed out that research his team has conducted in China also showed an increasing incidence of CLL. However, “on closer study, we found about two-thirds of cases were incidental, namely cases detected under circumstances [such as blood testing for a job].”
Shen-Miao Yang, MD, first author of that study, agreed and noted that improved treatment with drugs such as Bruton kinase inhibitors also can have the effect of increasing incidence – by extending lives.
“More patients are diagnosed, [and] receive the new agent, and their longer survival contributes to the increased burden of CLL,” Dr. Yang of People’s Hospital of Peking University, Peking University Institute of Hematology, Beijing, said in an interview.
Furthermore, “advanced techniques such as flow cytometry and fluorescence in situ hybridization are routinely used for the diagnosis and prognosis of CLL patients – that also increases the CLL burden.”
Dr. Yang had no disclosures to report. Dr. Gale disclosed that he is a consultant to BeiGene, Fusion Pharma, La Jolla NanoMedical, MingSight Pharmaceuticals, CStone Pharmaceuticals, NexImmune, and Prolacta Bioscience; an adviser to Antengene Biotech; medical director of FFF Enterprises; a partner of AZCA; member of the board of directors of the Russian Foundation for Cancer Research Support; and on the scientific advisory board of StemRad.