Abstract
Introduction: Survivors of Chronic Lymphocytic Leukemia (CLL) are at increased risk of second primary malignancies (SPM). Treatment of CLL has been transformed with the introduction of Targeted treatments with Bruton Tyrosine Kinase inhibitors in 2014 and BCL-2 inhibitors in 2016. Impact of the change in the treatment landscape and other environmental factors on the incidence of SPM and impact on racial & ethnic disparities in SPM is unknown. We analyze the risk of SPM in the pretarget treatment era 2000-2013 and Post target treatment era 2014-2022 stratified by Race and Ethnicity.
Methods: We analyzed data from the Surveillance, Epidemiology and End Results (SEER), Research Data 17 Registries, Nov 2024 Sub (2000-2022) to determine the risk of SPM in patients with an initial cancer diagnosis of CLL. With these criteria we had 42,906 patients with 386,770 patient years of follow up for pretarget treatment era and 32,634 patients with 121,687 patient years of follow up in the posttarget treatment era. The relative risk of subsequent malignancies is reported as a standardized incidence ratio (observed incidence [O]/expected incidence [E]). Results were stratified by Race and origin recode and analyzed.
Results: In the survivors of CLL there is an increasing incidence of SPM from pretargeted treatment era to the post 2014- targeted treatment era and remains high among all racial/ ethnic subgroups (Although confidence intervals overlap for some groups).
All patients Observed/ Expected (O/E) increased from 1.26 (CI: 1.24, 1.29) to 1.40 (CI: 1.35, 1.45)
Non-Hispanic White O/E increased from 1.27 (CI: 1.2, 1.30) to 1.40 (CI: 1.35, 1.46)
Hispanic all races O/E increased from 1.15 (CI: 1.04, 1.26) to 1.28 (CI: 1.09, 1.50)
Non-Hispanic Black O/E increased from 1.36 (CI: 1.24, 1.48) to 1.67 (CI: 1.46, 1.90)
Non-Hispanic American Indian/ Alaskan Native O/E increased from 1.23 (CI: 0.73, 1.95) to 3.33 (CI: 1.82, 5.59)
Non-Hispanic Asian/Pacific Islander O/E increased from 1.80 (CI: 1.56, 2.08) to 1.96 (CI: 1.53, 2.48)
In the post targeted treatment Era the cancers with the highest incidence ratio ( O/E) are Hodgkin's lymphoma 6.59 (CI: 4.38, 9.53), skin excluding basal and squamous malignancies ( 2.07 CI: 1.84, 2.32), urinary system 1.38 (CI 1.23, 1.54), Kidney 1.87(CI: 1.57, 2.21), Thyroid 2.33 (CI 1.77, 3.01), chronic myeloid leukemia 2.18 (CI 1.33- 3.36) and Acute Myeloid Leukemia 2.29 (CI 1.70- 3.03) .
Conclusions: Increasing incidence of second primary malignancy risk in the post 2014 targeted treatment era. This observation is consistent with other non-US based registry studies. This could be related to immune dysregulation with targeted treatments and other non treatment related factors. Racial/ethnic disparities persist in the post targeted treatment era and call for race conscious survivorship strategies.
