Risk factors for second primary malignancies (SPM) in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): A real-world study.

e19022 Background: Patients with CLL/SLL are at increased risk of developing SPM. Identification of key clinical risk factors associated with SPM is critical to inform long-term surveillance strategies and optimize disease management. Methods: Adult patients diagnosed with CLL/SLL from Jan 1, 2019 to May 31, 2023 were identified from the Symphony open claims database. Patients were categorized into three cohorts: (1) treated with first-line covalent BTK inhibitor (cBTKi), (2) treated with first-line chemoimmunotherapy (CIT), and (3) those who are managed with active observation. The 36-month incidence of SPM (excl. nonmelanoma skin cancer NMSC and hematologic malignancies HM) was estimated. Multivariable logistic regressions were used to assess associations between baseline characteristics (demographics; region; obesity; 3-factor risk estimate scale TRES, a validated comorbidity risk score; and select comorbidities) and SPM occurrence. Results: In total 86,654 patients with CLL/SLL were identified (cBTKi treated, n=11,352; CIT treated, n=12,589; and on active observation, n=62,713). Over 36-month follow-up, the incidence of SPM (excl. NMSC and HM) was 13.1% with cBTKi, 16.6% with CIT, and 11.8% managed with active observation ( P <.0001). In the overall population, age ≥70 yr (odds ratio OR, 1.43; 95% CI, 1.36-1.50), male sex (OR, 1.32; 95% CI, 1.26-1.38), higher TRES score (OR, 1.11; 95% CI, 1.05-1.18), chronic pulmonary disease (OR, 1.26; 95% CI, 1.19-1.34) and liver disease (OR, 1.30; 95% CI, 1.19-1.41) were independently associated with increased risk of SPM. Similar risk factors were identified when cBTKi, CIT, and patients on active observation, were assessed individually. Conclusions: Older age, male sex, higher disease burden, and chronic comorbidities were associated with increased SPM risk in patients with CLL/SLL. Treatment with CIT was linked to a higher SPM risk compared with cBTKi therapy or observation. Patients with these risk factors should be monitored for the development of SPM during CLL/SLL management. Risk factors, OR (95% CI) Overall CLL/SLL (N=86,654) cBTKi (n=11,352) CIT (n=12,589) Observation (n=62,713) Age (yr) ≥70 vs <70 1.43 (1.36-1.50) 1.35 (1.19-1.54) 1.22 (1.09-1.36) 1.52 (1.43-1.61) Sex Male vs female 1.32 (1.26-1.38) 1.33 (1.17-1.51) 1.19 (1.07-1.33) 1.34 (1.27-1.42) Race/ethnicity Non-Hispanic Black vs Non-Hispanic White 1.07 (0.99-1.16) 1.07 (0.87-1.30) 0.92 (0.75-1.12) 1.11 (1.01-1.23) Hispanic vs Non-Hispanic White 1.05 (0.95-1.16) 0.83 (0.61-1.13) 1.21 (0.98-1.49) 1.04 (0.92-1.17) TRES Scores 2-3 vs scores 0-1 1.11 (1.05-1.18) 1.25 (1.07-1.47) 1.24 (1.09-1.41) 1.05 (0.98-1.13) Select comorbidities Chronic pulmonary disease 1.26 (1.19-1.34) 1.13 (0.96-1.34) 1.22 (1.06-1.39) 1.29 (1.21-1.39) Liver disease 1.30 (1.19-1.41) 1.08 (0.82-1.42) 1.20 (1.01-1.43) 1.32 (1.18-1.47)