Incidence of Secondary Malignancies in CLL Patients on FCR Regimen in Central Europe
Chronic lymphocytic leukemia (CLL) represents the most common type of leukemia in Western countries with closely related incidence in Central European states. Since 2000, new therapeutic regimens have been explored and applied in an effort to improve patient prognosis, including the combination of fludarabine, cyclophosphamide, and rituximab (FCR). However, the development of new therapeutic regimens is also associated with concerns about the risk of secondary malignancies.
Treatment of CLL and Secondary Malignancies
In patients with CLL undergoing FCR regimen therapy, previously published studies have mostly reported an increased risk of melanoma and non-melanoma skin cancers (NMSC), acute myeloblastic leukemia (AML), and myelodysplastic syndrome (MDS). An increased risk of secondary malignancy development has also been observed in other malignancies, such as those of the breast, prostate, lungs, gastrointestinal tract, head, and neck.
Literary data documenting the incidence rate of secondary malignancies in these patients are, however, considerably limited. An international team from the Czech Republic, Hungary, and Poland has therefore published the first extensive study evaluating the incidence of secondary malignancies in patients with CLL on the FCR regimen (as well as the overall population of CLL patients) in Central Europe.
Study Objectives and Evaluated Population
The retrospective non-interventional study was conducted simultaneously in the Czech Republic (data collection period 2008–2016), Hungary (2004–2013), and Poland (2010–2015). The primary objective of the study was to evaluate the epidemiology and survival of CLL patients with secondary malignancies with specific focus on AML, MDS, and NMSC. The secondary objective was to identify key prognostic factors associated with the development of secondary malignancies.
In the entire population of patients with CLL amounting to 25,814 newly diagnosed cases, 10,312 patients (39.9%) underwent treatment. Among them, 1,986 (19.3%) received FCR regimen as first-line treatment, and 779 (7.6%) in subsequent lines. In the Czech Republic, nearly all patients underwent FCR therapy as the first-line treatment, while in other countries, it was comparably applied in first and subsequent lines of treatment. The number of newly diagnosed patients remained stable over the years, with annual mortality ranging from 5.9–9.3%.
Findings
A total of 33.7% of treated patients developed secondary malignancies during the study. In the Czech Republic, the incidence rate of secondary malignancies in the overall population of CLL patients was lower (22.9%), and the occurrence of secondary neoplasms in the treated population significantly differed across the countries.
For illustration − in the Czech Republic, the overall study population of CLL patients was 3,574 individuals, among whom AML developed in 4.1% (n = 145), MDS in 1.8% (n = 63), and NMSC in 1.2% (n = 44). The treated population in the Czech Republic comprised 941 patients, among whom secondary malignancies developed in 34.6% (n = 326), specifically AML in 2.9% (n = 27), MDS in 1.8% (n = 17), and NMSC in 2.1% (n = 20).
The diagnosis of AML was typically observed in patients younger than 60 years, while MDS and NMSC were diagnosed in individuals older than 70 years. In the overall study population of CLL patients, the most common secondary malignancy was leukemia (11%), followed by non-Hodgkin's lymphoma (10.8%), NMSC (3.8%), multiple myeloma (2.2%), and malignancies in the colon, sigmoid, and rectum (1.5%). Similar results were observed in the treated population of CLL patients.
The analysis observed a 28.0–36.8% probability of developing any secondary malignancy within 4 years from the initiation of FCR regimen therapy as first-line treatment. In the Czech Republic and Poland, the 5-year probability ranged from 29.9–36.4%. Key prognostic factors for developing secondary malignancy in CLL patients included age at diagnosis, male gender, previous malignancy in medical history, and CLL therapy. FCR regimen therapy was a statistically significant (p < 0.001) covariant of the increased risk of secondary malignancy in all three countries, with hazard ratios (HR) ranging from 1.46–1.60.
Conclusion
A consistent increased risk of secondary malignancies was observed in CLL patients on the FCR therapeutic regimen across the three Central European countries. The authors concluded that secondary malignancies are an underestimated risk in CLL patients, which should be considered when selecting and testing new therapeutic regimens.
(holi)
Source: Kósa F., Nečasová T., Špaček M. et al. Secondary malignancies and survival of FCR-treated patients with chronic lymphocytic leukemia in Central Europe. Cancer Med 2022 Oct 7, doi: 10.1002/cam4.5033 [Epub ahead of print].
Did you like this article? Would you like to comment on it? Write to us. We are interested in your opinion. We will not publish it, but we will gladly answer you.
