The survival of patients with chronic lymphocytic leukemia (CLL) has increased over the years. ‘Given this improvement, it is important to map out the long-term consequences for this group of patients,’ says Lina van der Straten (IKNL/Erasmus MC). Van der Straten and colleagues from various Dutch hospitals and IKNL therefore investigated the risk of a secondary primary tumor among patients with CLL, using data from the Dutch Cancer Registry (NKR). It appears that the risk of a secondary primary tumor among CLL patients is 63% higher compared to the general population.
This means that patients with a CLL have a 63% higher risk of developing a solid or haematological tumor (in addition to their CLL) than the risk of developing a (solid or haematological) tumor in the general population.
Secondary primary tumor can negate gains in life expectancy
Van der Straten: ‘Since more and more people with CLL are living longer, it is essential to understand the long-term effects of their disease and possible treatment. The development of secondary primary malignancies increases the burden of disease and care for patients and may offset the improvement in life expectancy of CLL patients. Therefore, awareness of the nature and extent of SPMs in CLL is essential not only for health-related planning such as choice of treatment or frequency of outpatient visits and imaging, but also for possible consideration of monitoring in patient follow-up for SPMs.’
Research design summarized
Van der Straten and colleagues looked at the risk standardized for age, sex and time period (SIR) and the absolute risk (AER) of an SPM. The researchers used data from the NKR of 24,815 CLL patients diagnosed between 1989 and 2019. They followed the patients until the diagnosis of the secondary primary tumor (SPM), death of the patient or end of follow-up. -up (December 31, 2019). The researchers identified the SPMs by re-matching patients to the NKR. The researchers looked at the risk for CLL patients in general, the risk based on gender, period of diagnosis (1989-1995, 1996-2002, 2003-2009, 2010-2019) or whether or not getting a treatment, and the risk of some specific cancers.
Van der Straten and colleagues excluded basal cell carcinomas of the skin in their study, because this registration is not complete over the entire study period. They also did not include diffuse large B-lymphoma and Hodgkin’s lymphoma, because almost all of those cases will involve transformed CLL, rather than a truly new malignancy. The researchers also excluded tumors that were diagnosed within 6 months after diagnosis of CLL, because in those cases it is difficult to say whether it is a secondary primary tumor or a synchronous primary tumor.
Increased risk especially among the elderly, men and treated patients
Van der Straten and colleagues found 4,700 SPMs in 4,369 CLL patients in a mean follow-up period of 6.2 years. That means that some patients developed multiple secondary primary tumors (for example, multiple squamous cell carcinomas in different locations). The risk of developing an SPM was 63% higher among the CLL patients than the age, gender and time period matched group from the general Dutch population. Compared to the general population, the risk is highest in patients younger than 70 years (SIR), but the absolute risk of an SPM is highest in patients between 70 and 80 years (AER). Patients older than 80 are less likely to develop an SPM because they often die before an SPM can develop. Patients who had been treated for their CLL within one year of diagnosis also had a higher risk of SPM compared to patients who had not been treated in that time: 212% increased vs. Increased 57%.
Risk of squamous cell carcinoma most increased
The researchers found an increased risk of both solid tumors (67% higher) and haematological malignancies (42% higher). In particular, the risk of skin tumors was significantly increased (squamous cell almost 5 times higher, melanoma almost 3 times higher), with subsequent acute myeloid leukemia (almost 3 times higher), soft tissue sarcomas and thyroid cancer (both more than 2 times as high) The risk of kidney cancer, primary tumor unknown, non-Hodgkin lymphomas, lung and bronchus cancer, and colon and rectal cancer was also increased. The risk of an SPM was higher among men with CLL than women, especially in squamous cell carcinoma (more than five times higher vs. almost 4 times higher. Van der Straten and colleagues saw that in the last two time periods studied (2003- 2009 and 2010-2019) the incidence of haematological malignancies increased.
Secondary primary tumor long-term effect of disease and treatment
For possible explanations for the increased risk of SPM among CLL patients, the researchers point, among other things, to the effects of the treatments for CLL. For example, the use of fludarabine-containing therapies is a likely explanation for the increase in haematological malignancies described by Van der Straten and colleagues. Also, the disruptive characteristics of CLL on the immune system may enhance the effect of common carcinogens (such as UV radiation and smoking). The particularly increased risk of squamous cell carcinoma among men in particular could be explained by the fact that men work outside more often and are more exposed to UV radiation throughout their lives, the researchers believe.
More information
Contact Lina van der Straten, researcher, or view the full article:
- van der Straten, L., Levin, M. D., Dinnessen, M. A., Visser, O., Posthuma, E. F., Doorduijn, J. K., … & Dinmohamed, A. G. (2023). Risk of second primary malignancies in patients with chronic lymphocytic leukemia: a population-based study in the Netherlands, 1989-2019. Blood Cancer Journal, 13(1), 1-10.