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e19027 Background: The International Workshop on CLL recommends testing patients (pts) with CLL/SLL for deletion 17p (del17p) and tumor protein (TP) 53 mutations for prognosis and treatment decisions. Both Bruton Tyrosine Kinase inhibitors (BTKi) and B-cell lymphoma 2 protein inhibitor (BCL2i) are approved as effective frontline therapies for CLL/SLL pts, particularly those with high-risk features such as del17p and TP53. However, there is no clinical study directly comparing the efficacy of BTKi and BCL2i. We sought to understand the real-world use of BTKi and BCL2i as well as the differences in time to next treatment, a surrogate for progression-free survival, among CLL/SLL pts who were identified as having either del17p or TP53 mutations and treated with a BTKi or BCL2i in the 1L setting. Methods: We used the Integra Connect PrecisionQ real-world de-identified database of over 3 million cancer pts across 500 sites of care to identify CLL/SLL pts for the analysis. We observed pts who started 1L treatment between 3/4/2016 and 12/4/2023. Risk status was captured via medical chart curation to determine the presence del17p or TP53 mutations. Time to next treatment was measured from the treatment start to the first of the initiation of a subsequent line of therapy or death. Descriptive analyses were used and time to next treatment was analyzed using a Kaplan Meier analysis. Results: We identified 295 CLL/SLL pts with high-risk features. The median (IQR) age of these pts at treatment start was 74 (66,81) years old, 62% were male, 77% identified as White, 8% as African American, and 15% as Other. Of these high-risk pts, 72% had only a deletion 17p, 13% had only TP53 mutation, and 15% had both. The percent of high-risk pts who received a BTKi in 1L was 69% with a median (IQR) age of 75 (65, 81) at treatment start, while 13% received a BCL2i in 1L with a median (IQR) age of 70 (64,77) at treatment start. The percent of pts who received neither a BTKi or BCL2i in 1L was 18% with median (IQR) age of 74 (68,80) at treatment start. The median time to next treatment for those who received a BTKi was 68.4 months (95% Confidence Interval CI: 48.4, NA) compared to 45.5 months (CI: NA, NA) for pts who received a BCL2i. The median (IQR) duration for patients treated with a BCL2i +/- obinutuzumab was 396 (285,603) days. The probability of pts who did not initiate a next treatment at 30 months was found to be 71% (95% CI, 64% to 78%) for those who received a BTKi (p <0.05) compared to 92% (95% CI, 83% to 100%) for those who received a BCL2i. Conclusions: The real-world data comparison of 1L treatment in high-risk pts with CLL/SLL shows that, after 30 months, the probability of not initiating the next treatment is 92% for those treated with a BCL2i compared to 76% for those treated with a BTKi. Additional follow-up and a larger sample may be needed to further validate these findings.
Hou et al. (Sat,) studied this question.