1148 - Time to treatment initiation in 17p-deleted Chronic Lymphocytic Leukemia has no influence on overall survival

Objectives: In chronic lymphocytic leukemia (CLL), chromosome 17 p deletion (del17p) occurs in 8.5% of all newly diagnosed with CLL with an inferior median overall survival (OS) of 2 to 3 years from time of first-line treatment versus 7 – 8 years in those without del17p (Dohner et al 2000). However, when there are no indications to initiate treatment as per the iwCLL criteria, testing for del17p alters the “wait and watch” strategy to “wait and worry”. Despite this understanding, TP53 mutation or chromosome 17p del detection is a part of many standard CLL diagnostic panel testing. Therefore, our objective was to evaluate the testing patterns for del17 by Fluorescence in situ hybridization (FISH) and determine the influence of time to treatment initiation (TTTI) in patients (pts) with untreated CLL and del17p on overall survival.

Methods: Data was collected from the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database. The Flatiron Health database is a longitudinal database, comprising de-identified patient-level structured and unstructured data, curated via technology-enabled abstraction. During the study period, the de-identified data originated from approximately 280 cancer clinics (~800 sites of care). Inclusion criteria included pts diagnosed with CLL between January 1991 to October 2021 and with a follow up of more than 90 days with at least two visits documented in the EHR. Del17p status was the predictor variable, and the primary endpoint was real-world overall survival (rwOS). TTTI was defined as time from diagnosis to time of first treatment initiation and censored if death prior to treatment. First, Kaplan and Meier method was used to describe the effect of del17p status (del17p v non-del17p) on rwOS and compared using the log rank test from the date of diagnosis to the date of death. Second, to evaluate the influence of del17p status on rwOS adjusted for TTTI, we used the index date as the date of diagnosis with the date of treatment initiation as a time-varying covariate and compared using cox regression model. Lastly, we evaluated the influence of TTTI on rwOS in del17p CLL measured from the time of diagnosis to the time of death with the date of treatment initiation as a time-varying covariate and compared using cox regression model. All patients were followed up until the relevant event of interest (death) or censored at their last structured activity in the EHR, defined as a documented office visit, vital status measurement, or medication administration.

Results: Out of 13,713 patients with CLL who met the inclusion criteria, 9745 (71%) patients had FISH analysis performed. Of these, 5455 (56%) pts had testing done within 3 months of diagnosis. In pts with FISH analysis done within 3 months of diagnosis, 595 pts had del17p present (4079 non-del17p and 781 unk) with a median age at diagnosis of 67 years (IQR 59-74). The median follow-up time by reverse Kaplan Meier method was 6 yrs (IQR 3.5 – 9.4). The median TTTI was 3 months (95%CI 3-5) for del17p and 11 months (95%CI 10 – 12) for non-del17p. The median rwOS for del17p was 6.7 yrs. (95%CI 5.6 – 7.2) compared to 11.4 yrs. (95%CI 11 – 12.6) for non-del17p CLL (p < 0.0001). The presence of del17p CLL had inferior rwOS despite adjusting for TTTI compared to non-del17p CLL with HR of 1.99 (95%CI 1.8 – 2.2). In patients with del17p CLL, TTTI had no influence on rwOS with HR of 1.1 (95%CI of 0.58 – 2.19).

Conclusion: Approximately one-third of newly diagnosed CLL patients do not have FISH analysis performed and when done, half of all the FISH analysis are done within the first three months of diagnosis. The presence of del17p confers an inferior survival compared to non-del17p. Pts with del17p have a shorter TTTI however time to treatment initiation does not influence rwOS. Therefore, FISH testing at diagnosis for asymptomatic patients may not aid in guiding treatment decisions and may be considered only when symptomatic or when treatment is indicated.