Interested in more data about venetoclax-based and fixed-duration regimens in CLL? Be sure to check out John N. Allan, MD, discuss data of each approved fixed-duration CLL regimen.2
How was the real-world analysis of TLS in MCL and CLL designed?
Real-World TLS Risk With Venetoclax in CLL and MCL
- Median time to TLS mortality for patients with CLL and MCL were 47 and 43 days, respectively
- 3-month TLS risk was higher in MCL (8.6%) than CLL (5.6%) by the ICD-10-CM–based definition
- Most patients in each group received venetoclax monotherapy and were at least 65 years of age.
Investigators used deidentified electronic health record data from the TriNetX Dataworks-USA Network to identify patients with CLL or MCL who began venetoclax treatments between April 11, 2016, and December 31, 2024.1
The real-world analysis included patients with at least 1 medical record within 1 year prior to the index date and at least 2 diagnosis codes for CLL or MCL recorded at least 14 days apart, with the first code being recorded on or before the index date.
If patients had a TLS diagnosis on or before the index date, a data error such as a death date preceding the index date, or a diagnosis code indicating clinical trial participation, they were not included in the analysis.
Follow-up extended for 3 months to capture the venetoclax dose ramp-up period, with death treated as a competing risk for the TLS outcome.1 Secondary end points were, cumulative incidence of mortality among patients with TLS with death from other causes treated as a competing event.
Patients with CLL and MCL had a both had a median age of 69 years (interquartile range, 62-76) and were predominantly White (CLL, 83.3%; MCL, 82.8%) and male (66.3%; 71.1%). Most patients in the CLL group were at least 65 years old (68.7%), similar to the MCL group (67.2%). Regarding Charleston Comorbidity Index scores, 54.1% of patients with CLL and 55.9% of patients with MCL had an index of at least 1. Hypertensive disease was the most common baseline comorbidity in both cohorts (42.6%; 42.9%), followed by heart disease (33.1%; 33.3%), kidney disease (20.5%; 22.5%), and diabetes mellitus (15.8%; 13.5%).
Venetoclax was administered in combination with rituximab (Rituxan) or obinutuzumab (Gazyva) in 44.3% of patients with CLL and 40.7% of patients with MCL, with the remainder receiving venetoclax monotherapy.
What was the risk of mortality among patients who experienced TLS?
By incidence rate, mortality among patients with TLS occurred at 0.1 events per 100 patient-months (95% CI, 0.1-0.2) in the CLL cohort and 0.8 events per 100 patient-months (95% CI, 0.4-1.6) in the MCL cohort. Incidence rates per 100 patient-months for the ICD-10-CM-based TLS definition were 2.0 (95% CI, 1.8-2.3) and 3.4 (95% CI, 2.4-4.7) among patients with CLL and MCL, respectively. Respective incidence rates with the rasburicase use-based definition for those with CLL and MCL were 1.4 (95% CI, 1.2-1.6) and 2.3 (95% CI, 1.5-3.4).
References
- Ferrajoli A, Zhou L, Ali A, et al. CLL-737: Risk of Tumor Lysis Syndrome Among Patients With Chronic Lymphocytic Leukemia or Mantle Cell Lymphoma Treated With Venetoclax: A Real-World Study. Clinical Lymphoma Myeloma and Leukemia. 2026;26:S617. doi:/10.1016/S2152-2650(26)02060-4.
- Allan JN. Have fixed-duration (FD) regimens delivered on their promise in chronic lymphocytic leukemia and what is the future of FD regimens? a narrative review. Adv Ther. 2026;43(3);1034-1059. doi:10.1007/s12325-025-03486-z