A Multicenter Retrospective Study to Understand the Clinical Characteristics, Treatment Patterns, and Resource Utilization for Patients with Chronic Lymphocytic Leukemia: CREEK Study
Authors: Alhuraiji Ahmad , Alhejazi Ayman , Samra Mohamed , Bagal Bhausaheb , Pavlovsky Miguel Arturo , Roa Macarena , Wu Shang-Ju , Montano Figueroa Efreen H , Selvaratnam Veena , Lin Chee-Yen , K Pushpalata , Ishikawa Akemi , Gonzalez Hernandez Francisco 
Published: December 2023

Abstract
Introduction: The ever-growing array of treatments available for chronic lymphocytic leukemia (CLL) led to a significant change in CLL management over the last few years. However, information about managing CLL is scattered across various regions, resulting in significant disparities in treatment approaches and patient outcomes between countries. The CREEK study aimed to describe the disease characteristics, treatment patterns, and overall survival (OS) among CLL-treated (CLL-Tx) patients and CLL treatment-naïve (CLL-N) patients in different regions.
Methods: Data from 1009 patients were collected retrospectively from June 2016 to March 2023. This observational study included 886 CLL-Tx patients from 17 countries in the Middle East and Africa (MEA), Asia Pacific (AP), and Latin America (LA); and a pilot cohort of 123 CLL-N patients from the Gulf Cooperation Council (GCC) countries. Patients' demographics, disease characteristics, laboratory assessments, comorbidities, treatment patterns, treatment-related adverse events (AEs), OS, and medical resource utilization (MRU) data were recorded.
Results: The average age for both cohorts was 63 years. Most patients were males, 66.7% in CLL-Tx and 69.9% in CLL-N. The mean duration from clinical manifestation until diagnosis was 21.37 months for CLL-Tx and 1.46 months for CLL-N patients (p&lt;0.0001). For CLL-Tx, almost 62% of the patients in MEA, 59.3% in AP, and 68.8% in LA had an Eastern Cooperative Oncology Group (ECOG) score of 0 or 1, and similarly for CLL-N patients (56.1%). Total leucocytic count, lymphocytes, and platelets showed a significant difference (p&lt;0.05) between CLL-Tx and CLL-N patients. As per the Cumulative Illness Rating Scale (CIRS), musculoskeletal (p&lt;0.0008) and endocrine-metabolic (p&lt;0.0001) comorbidities were more frequent in the CLL-Tx group. Regarding the CLL-Tx patients, 69.7%, 62.9%, and 41.1% had extremely severe hematological problems (CIRS score 4) in MEA, LA, and AP, respectively. At diagnosis, patients from the MEA region presented with the highest prevalence of advanced disease staging, with 44.8% and 35.3% based on Rai and Binet Staging Scores, respectively; moreover, CLL-Tx patients exhibited a more advanced staging compared to CLL-N based on the same scores (p &lt;0.0001). FISH testing for disease prognosis was not performed in about 59% of the patients across all regions. The testing rates for cytogenetic abnormalities, IGHV mutation status, and TP53 aberrations were relatively low in all regions. The percentage of unmutated IGHV was considerably higher (p=0.0001) in CLL-Tx (15.6%) patients, with the highest percentage in LA (21.0%), compared to CLL-N (10.6%). Cytogenetic abnormalities did not show significant differences between CLL-Tx and CLL-N patients (p&gt;0.05), while TP53 aberrations differ significantly (p&lt;0.05) (Table 1). Most patients, 76.0%, 81.8%, and 69.4%, received chemo-immunotherapies as 1 st line therapy, while 18.3%, 17.1%, and 30.1% received targeted therapy in MEA, AP, and LA, respectively. The percentage of patients with AEs who received 1 st line chemo-immunotherapies was higher than those who received targeted therapy (25.6% vs. 7.3%). The mean OS was 153.89 months in the treated study population (Table 2). The mean number of inpatient hospitalizations was 1.9 times for chemo-immunotherapy and 0.8 times for targeted therapy. The mean lengths of stay of 14.9 and 13.9 days, respectively; mean emergency room visits were 0.5 and 0.7, and blood transfusions were received by 16.7% and 9.2% of patients, respectively.
Conclusions: This study highlights the variable disease characteristics between CLL-Tx and CLL-N patients and provides insight into the regional variations in treatment patterns and OS for CLL-Tx patients. A considerable number of patients had advanced disease staging at diagnosis; however, the study showed relatively low genetic testing rates, indicating the need for adequate clinical watchfulness. Despite being in the era of approved targeted therapy, the utilization of chemo-immunotherapy continues to be higher than that of targeted therapy in the first line, probably due to the lower access to targeted therapies.
Keywords: Chronic Lymphocytic Leukemia (CLL), Genetic Testing, Treatment Patterns, Targeted Therapy, Chemo-immunotherapy, Real World Data.