Systematic Review of Real-World Data on the Effectiveness and Safety Profiles of First-Line Therapies in Chronic Lymphocytic Leukemia
Author(s)
Anita Stozek-Tutro, MSc1, Monika Malowicka, MSc2, Klaudia Janiszewska, MSc2, Pawel Kawalec, PhD, MD3.
1Jagiellonian University Medical College, Kraków, Poland, 2HTA Consulting, Kraków, Poland, 3Institute of Public Health, Jagiellonian University, Kraków, Poland.
1Jagiellonian University Medical College, Kraków, Poland, 2HTA Consulting, Kraków, Poland, 3Institute of Public Health, Jagiellonian University, Kraków, Poland.
OBJECTIVES: To investigate the real-world effectiveness and safety profiles of targeted therapies—such as venetoclax+obinutuzumab (VEN+OBI), ibrutinib (IBR), zanubrutinib (ZAN), acalabrutinib (ACA), and other first-line treatment options—for chronic lymphocytic leukemia (CLL), and to compare these real-world data (RWD) with outcomes reported in randomized controlled trials (RCTs).
METHODS: A systematic review was performed to identify RWD by searching MEDLINE, EMBASE, and the reference lists of eligible studies (search date: January 2, 2025; CRD42024549185). Key clinical endpoints included progression-free survival (PFS), overall survival (OS), time-to-next treatment (TTNT), and treatment discontinuation due to adverse events (TdAE). RCTs used for comparison were identified based on previous systematic reviews.
RESULTS: A total of 37 observational studies met the inclusion criteria. IBR was the most extensively evaluated agent and demonstrated consistent real-world effectiveness, closely reflecting RCT outcomes (RESONATE-2), with 24-month OS rates of 82-96% and PFS rates of 68-96%. ZAN, reported in a single study, showed a 36-month OS of 93% and a PFS of 87%, aligning with the SEQUOIA trial. No real-world OS or PFS data were identified for VEN+OBI and ACA. However, ACA demonstrated a 24-month TTNT rate of 88%, consistent with ELEVATE-TN outcomes. Data on VEN+OBI were limited but suggested a 24-month TTNT of 77%, slightly lower than in the CLL-14 trial. In contrast, idelalisib+rituximab (IDE+RTX) was associated with lower 24-month OS (77%) and PFS (72%), and the highest TdAE rate (63%). No RWD were available for other therapies.
CONCLUSIONS: Among first-line therapies for CLL, IBR has the most extensive and consistent RWD, with results closely reflecting those from RCTs. ZAN and ACA show promising outcomes, while data for VEN+OBI remain limited. IDE+RTX appears less favorable in terms of real-world effectiveness. These findings highlight the growing value of RWD in complementing RCTs and emphasize the need for more robust RWD, particularly for newer agents.
METHODS: A systematic review was performed to identify RWD by searching MEDLINE, EMBASE, and the reference lists of eligible studies (search date: January 2, 2025; CRD42024549185). Key clinical endpoints included progression-free survival (PFS), overall survival (OS), time-to-next treatment (TTNT), and treatment discontinuation due to adverse events (TdAE). RCTs used for comparison were identified based on previous systematic reviews.
RESULTS: A total of 37 observational studies met the inclusion criteria. IBR was the most extensively evaluated agent and demonstrated consistent real-world effectiveness, closely reflecting RCT outcomes (RESONATE-2), with 24-month OS rates of 82-96% and PFS rates of 68-96%. ZAN, reported in a single study, showed a 36-month OS of 93% and a PFS of 87%, aligning with the SEQUOIA trial. No real-world OS or PFS data were identified for VEN+OBI and ACA. However, ACA demonstrated a 24-month TTNT rate of 88%, consistent with ELEVATE-TN outcomes. Data on VEN+OBI were limited but suggested a 24-month TTNT of 77%, slightly lower than in the CLL-14 trial. In contrast, idelalisib+rituximab (IDE+RTX) was associated with lower 24-month OS (77%) and PFS (72%), and the highest TdAE rate (63%). No RWD were available for other therapies.
CONCLUSIONS: Among first-line therapies for CLL, IBR has the most extensive and consistent RWD, with results closely reflecting those from RCTs. ZAN and ACA show promising outcomes, while data for VEN+OBI remain limited. IDE+RTX appears less favorable in terms of real-world effectiveness. These findings highlight the growing value of RWD in complementing RCTs and emphasize the need for more robust RWD, particularly for newer agents.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO232
Topic
Clinical Outcomes, Real World Data & Information Systems
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Oncology, Rare & Orphan Diseases