Contributions
Abstract: EP637
Type: E-Poster Presentation
Session title: Chronic lymphocytic leukemia and related disorders - Clinical
Background
The longevity of patients with chronic lymphocytic leukemia (CLL) improved progressively over the past decades due to efficacious therapies in the upfront and relapsed/refractory setting. The downside of this improved longevity is the development of second primary malignancies (SPMs), which, in turn, may attribute to morbidity and excess mortality in CLL patients. Therefore, awareness of the magnitude of SPMs in CLL is essential for health-related planning and surveillance activities.
Aims
In this nationwide, population-based study, we assessed the risk of SPM development in CLL patients diagnosed in the Netherlands compared with the general Dutch population.
Methods
We selected all CLL patients diagnosed in the Netherlands between 1989-2018 from the Netherlands Cancer Registry. To counteract surveillance bias, an SPM was defined as a malignancy occurring at least six months after CLL diagnosis. Of note, transformations were regarded as the same entity as the primary tumor and basal cell carcinomas were excluded from the analysis since they were not registrated nationwide throughout the entire study period. CLL patients were followed from the date of diagnosis to SPM development, death, or end of follow-up (December 31, 2018, whichever occurred first). Standardized incidence ratios (SIRs)—with associated 95% confidence intervals (CIs)—were calculated using the exact Poisson method as the ratio of the observed malignancies in the CLL population and the expected malignancies in an age-, sex-, and period-matched group from the general population.
Results
A total of 23,622 CLL patients (61% males; median age 69 years) were included in this analysis, of whom 4,062 (17%) subsequently developed an SPM after a median follow-up time of 4 years (IQR:1-8 years). Overall, the risk of SPMs in CLL patients was 64% higher than in the general population (SIR 1.64; 95% CI: 1.59-1.69; Figure 1). The increased risk was observed both for solid (SIR 1.72; 95%CI 1.66-1.77) and hematological malignancies (SIR 1.24; 95%CI 1.11-1.37) with no sex-related differences. However, patients aged 18-60 were more at risk for the development of an SPM (SIR 1.88; 95%CI 1.76-2.01) as compared to patients aged above 60 years (SIR 1.58; 95%CI 1.52-1.63). The overall risk of solid SPMs was significantly heightened for the following sites (in order of increasing risk): skin (squamous cell and melanoma), kidney and renal, primary site unknown, lung, colon and rectum and prostate. As for hematological malignancies, the risk of developing acute myeloid leukemia (AML) was significantly increased compared to the general population. Conversely, myeloproliferative neoplasms were less frequently observed than in the general population (Figure 1).
Conclusion
In this nationwide, population-based study, we demonstrated that CLL patients have an increased risk of developing various SPMs compared to the general population. SPMs in CLL may originate from shared pathophysiological factors, environmental exposures, host characteristics, or some combination of the three. In addition, CLL-related therapy could have attributed to the development of an SPM, particularly in AML. Collectively, our study findings can be used in the communication between patient and physician about appropriate surveillance activities and interventions to counteract the increased morbidity and excess mortality associated with SPMs. The current study serves as a benchmark to assess how the spectrum of SPMs may alter in a contemporary era with chemo-free treatment options.
Keyword(s): Chronic lymphocytic leukemia, Malignancy, Population
Abstract: EP637
Type: E-Poster Presentation
Session title: Chronic lymphocytic leukemia and related disorders - Clinical
Background
The longevity of patients with chronic lymphocytic leukemia (CLL) improved progressively over the past decades due to efficacious therapies in the upfront and relapsed/refractory setting. The downside of this improved longevity is the development of second primary malignancies (SPMs), which, in turn, may attribute to morbidity and excess mortality in CLL patients. Therefore, awareness of the magnitude of SPMs in CLL is essential for health-related planning and surveillance activities.
Aims
In this nationwide, population-based study, we assessed the risk of SPM development in CLL patients diagnosed in the Netherlands compared with the general Dutch population.
Methods
We selected all CLL patients diagnosed in the Netherlands between 1989-2018 from the Netherlands Cancer Registry. To counteract surveillance bias, an SPM was defined as a malignancy occurring at least six months after CLL diagnosis. Of note, transformations were regarded as the same entity as the primary tumor and basal cell carcinomas were excluded from the analysis since they were not registrated nationwide throughout the entire study period. CLL patients were followed from the date of diagnosis to SPM development, death, or end of follow-up (December 31, 2018, whichever occurred first). Standardized incidence ratios (SIRs)—with associated 95% confidence intervals (CIs)—were calculated using the exact Poisson method as the ratio of the observed malignancies in the CLL population and the expected malignancies in an age-, sex-, and period-matched group from the general population.
Results
A total of 23,622 CLL patients (61% males; median age 69 years) were included in this analysis, of whom 4,062 (17%) subsequently developed an SPM after a median follow-up time of 4 years (IQR:1-8 years). Overall, the risk of SPMs in CLL patients was 64% higher than in the general population (SIR 1.64; 95% CI: 1.59-1.69; Figure 1). The increased risk was observed both for solid (SIR 1.72; 95%CI 1.66-1.77) and hematological malignancies (SIR 1.24; 95%CI 1.11-1.37) with no sex-related differences. However, patients aged 18-60 were more at risk for the development of an SPM (SIR 1.88; 95%CI 1.76-2.01) as compared to patients aged above 60 years (SIR 1.58; 95%CI 1.52-1.63). The overall risk of solid SPMs was significantly heightened for the following sites (in order of increasing risk): skin (squamous cell and melanoma), kidney and renal, primary site unknown, lung, colon and rectum and prostate. As for hematological malignancies, the risk of developing acute myeloid leukemia (AML) was significantly increased compared to the general population. Conversely, myeloproliferative neoplasms were less frequently observed than in the general population (Figure 1).
Conclusion
In this nationwide, population-based study, we demonstrated that CLL patients have an increased risk of developing various SPMs compared to the general population. SPMs in CLL may originate from shared pathophysiological factors, environmental exposures, host characteristics, or some combination of the three. In addition, CLL-related therapy could have attributed to the development of an SPM, particularly in AML. Collectively, our study findings can be used in the communication between patient and physician about appropriate surveillance activities and interventions to counteract the increased morbidity and excess mortality associated with SPMs. The current study serves as a benchmark to assess how the spectrum of SPMs may alter in a contemporary era with chemo-free treatment options.
Keyword(s): Chronic lymphocytic leukemia, Malignancy, Population