Introduction: There is an unmet need to understand how novel therapies translate into real-world clinical practice for CLL, particularly in resource-limited regions. The CREEK study (NCT04964908) aimed to describe clinicodemographic characteristics and treatment patterns in patients with CLL.

Methods: The LATAM (Latin America) cohort of this retrospective, observational, registry-based study collected data from 8 countries (AR, BR, CL, CO, CR, DO, PA, MX) in patients with CLL (aged ≥18 years) from Jun 2016 to Mar 2023 with ≥12 months of follow-up data available from the start of the treatment (except in case of death in <12 months). Primary endpoints included clinicodemographic characteristics. Secondary endpoints were treatment patterns per line of therapy (LOT), progression-free survival [PFS], time to treatment failure [TTF]), time to new treatment [TTNT], and adverse events (AEs). Exploratory outcomes included overall survival (OS) and medical resource utilization (MRU). Survival parameters were calculated by Kaplan-Meier method with 95% CI.

Results: Of 186 patients (median age: 69.0 years [range: 31-90]) included, 58.1% (108/186) were males, 38.1% (53/139) were current/ex-smokers, 3.2% (6/186) had family history of haematological malignancies and 8.1% (15/186) had other concomitant malignancy. Per available data, 68.8% (128/140) had an ECOG score of ≤1 at the time of treatment/diagnosis. At treatment/diagnosis and follow-up, per CIRS, 98.3% (117/119) and 98.2% (110/112) patients reported extremely severe haematological problems, concomitant medications use at diagnosis/treatment was reported in 64.5% (120/186) and at follow-up in 61.3% (114/186) patients. Around 30.7% (43/140) patients had stage III/IV Rai Staging and 54.4% (87/160) had Stage B/C Binet Staging score. FISH testing results for disease prognosis were available for 41.4% (77/186) patients. The testing rates for cytogenetic abnormalities, IGHV mutation status, and TP53 aberrations were 13.7% (25/179), 42.6% (29/68) and 12.2% (5/41). In those with cytogenetic abnormalities, 56% (14/25) had del (17p), 20% (5/25) had del (11q) and 32% (8/25) had complex karyotype. The median duration from clinical manifestation until diagnosis was 23.5 (0-251.8) months. Immediate therapy was received by 37.0% (64/173) patients, and the median time of observation was 1038 (15-7663) days. In 1st LOT (n=186), 69.7% (129/185) patients (received chemo-immunotherapy (CIT); 30.3% (56/185) received targeted therapies (ibrutinib, rituximab, venetoclax, obinutuzumab) with median treatment duration of 157 days. In 2nd LOT (n=48) with 65.2% (30/48) received CIT and 34.8% (16/46) received targeted therapy with median treatment duration of 124 days. <1% patients received 3rd, 4th and 5th LOT; of these, majority (>55%) received CIT. The mean OS was 163.7 months; with 97.3% (n=181) patients alive at the time of data collection, median OS was not evaluable. In 1st LOT, the median PFS, TTF and TTNT (in months [95% CI]) for CIT were 58.1 (15.9-NE), 5.3 (3.8-7.0) and 14.5 (6.5-32.7). For targeted therapy, median PFS was not reached in 1st LOT; median TTF was 5.4 months (95% CI: 5.2-NE). The mean emergency room visits were 0.6±1.34 and 1.3±3.61 and blood transfusions were received by 15.5% (20/129) and 3.6% (2/56) of patients receiving CIT and targeted therapy, respectively. Regardless of the LOT, overall, 40.3% (75/186) patients reported AEs with 12.8% (23/179) reporting severe AEs. The percentage of patients with AEs who received targeted therapy (62.5%) was higher than those who received CIT (34.9%).

Conclusion: In CREEK-LATAM cohort of CLL-treated patients, most patients had an advanced disease at diagnosis. Despite being from large academic centres, we found limited access to genetic testing contributed to low rates of genetic testing, which underscores the need to understand associated factors in terms of lack of awareness of its prognostic importance, and concerns about its complexity. CIT remains the predominant 1st LOT with <1/3rd receiving targeted therapy, despite the availability of targeted therapies at the time of the study. Larger scale studies are required to check efficacy and safety of treatment options for CLL. CIT is associated with a higher proportion of AEs and MRU than targeted therapies, highlighting the need for tailored approaches to improve CLL outcomes.

Acknowledgement: Authors would like to thank Ria Vijay (Fortrea Scientific Pvt Ltd) for medical writing assistance.

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2025
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