Venetoclax Treatment Outcomes and Patterns of Use in Relapsed/Refractory Chronic Lymphocytic Leukemia Under Routine Clinical Practice in Saudi Arabia and Gulf Countries (VICTORY Study)

Background: Chronic lymphocytic leukemia (CLL) is a CD5+ B-cell malignancy with a substantial burden in Saudi Arabia and Gulf countries. Patients in this region are treated primarily in tertiary care centers, where clinically relevant cytogenetic and molecular testing is performed. Despite the importance of these tests (eg, 17p deletion, TP53 mutations, and IGHV mutational status) in predicting disease prognosis and treatment selection, they are not available to all physicians in all centers. This variance may potentially influence treatment sequence and consequently affect treatment outcomes.

Additionally, physicians generally follow international guidelines (eg, ESMO and NCCN) or adopt center-specific treatment algorithms because there are no local treatment guidelines. The clinical efficacy and tolerability of venetoclax monotherapy or venetoclax combination with the anti-CD20 monoclonal antibody rituximab has been proven in clinical trials. The clinical trial setting is usually different than real world practice in terms of diagnostic tests, follow up schedules, and medication use, making it essential to study the treatment-related outcomes in routine clinical practice. This analysis is among the first conducted in Saudi Arabia and Gulf countries to investigate the use of a novel agent in treating CLL.

Methods: This was a non-interventional, multicenter, retrospective cohort study investigating real-world treatment outcomes and patterns of use of venetoclax regimens (venetoclax monotherapy or venetoclax in combination with rituximab) in patients with relapsed/refractory CLL under routine practice in Saudi Arabia (5 sites) and Gulf countries (United Arab Emirates [2 sites], and Kuwait [1 site]). Eligible patients were aged ≥18 years with relapsed/refractory CLL treated with any venetoclax regimen for ≥3 months. Data were collected from patients' medical records. The primary endpoint was best overall response rate (ORR; defined as complete response [CR], CR with incomplete bone marrow recovery, nodular partial response [PR], or PR) of venetoclax regimens according to physician assessment. Secondary endpoints included the dose and schedule of venetoclax regimens used, number of prior lines of therapy, overall survival (OS) and progression-free survival (PFS) on venetoclax monotherapy and venetoclax plus rituximab, adverse events (AEs) observed during treatment with venetoclax regimens, as well as patient demographics and prognostic factors testing.

Results: A total of 48 patients were analyzed in this study. The mean (SD) age at the start of venetoclax treatment was 58.3 (12.5) years. In total, 31.1% of patients (n=15) had reported del17p and/or TP53 test results; among those, 33.3% (n=6) were positive for del17p deletions and/or TP53 mutation. ORR (95% CI) was 85.4% (75.4%-95.4%), median (range) time to the first recorded response was 2.0 (0-10) months and median (range) time to best response was 5.0 (0-35) months. Venetoclax plus rituximab was used in 56.3% (n=27) of patients, and venetoclax monotherapy was used in 43.8% (n=21). The majority of patients were treated with a full dose of venetoclax (400 mg [77.1%; n=37]), followed by 200 mg (10.4%; n=5), 100 mg, and 300 mg (both 6.3%; n=3 each). There was a median (range) of 1 (1-5) prior lines of treatment. The median (range) duration of follow-up was 13.5 (3.0-38.0) months. Median OS was not reached (Figure 1), and median (95% CI) PFS was 24.0 (20.4-30.7) months (Figure 2). Overall, 31.3% (n=15) of patients reported an AE during treatment and serious AEs occurred in 10.4% (n=5) of patients. Grade ≥3 neutropenia and thrombocytopenia were reported in 7 (14.6%) and 2 (4.2%) patients, respectively. No patients developed tumor lysis syndrome. Two patients (4.2%) discontinued treatment due to toxicity.

Conclusions: In this retrospective study of patients with relapsed/refractory CLL in Saudi Arabia and Gulf countries, the use of venetoclax regimens is associated with a high ORR and a tolerable safety profile, supporting favorable outcomes for real-world venetoclax use in this region.

Alfayez:Amgen: Honoraria; AbbVie: Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria; Astellas: Honoraria; AstraZeneca: Honoraria, Research Funding; Johnson & Johnson: Honoraria; Celgene: Research Funding. El Ashal:RAY CRO: Current Employment. Hussein:RAY CRO: Current Employment. Anwar:AbbVie, Inc: Current Employment, Current equity holder in publicly-traded company. Ismail:AbbVie, Inc: Current Employment, Current equity holder in publicly-traded company. Bereksi:AbbVie, Inc: Current Employment, Current equity holder in publicly-traded company. Abdellatif:AbbVie, Inc: Current Employment, Current equity holder in publicly-traded company. Nour:AbbVie, Inc: Current Employment, Current equity holder in publicly-traded company. Saad:AbbVie, Inc: Current Employment, Current equity holder in publicly-traded company.