BACKGROUND: Targeted therapies are the standard approach within the treatment landscape for chronic lymphocytic leukemia (CLL), yet it continues to evolve from treat-to-progression (TTP) approaches toward fixed-durationregimens. This evolution presents new challenges for clinicians tasked with incorporating emerging data and evidence-based guidelines into individualized care plans. This multi-phase educational initiative was developed to assess treatment patterns, clinical preferences, and decision-making challenges in CLL management; particularly in community settings, where variability in resources and care models exists.

METHODS: As part of this initiative, Medlive conducted a national survey of clinicians managing patients with CLL, administered between February and March 2025 in partnership with IQVIA, which assisted in identifying and verifying clinicians managing patients with CLL using ICD-10 coding data. The survey aimed to capture insights into current treatment patterns, therapeutic preferences, and operational barriers in both frontline and relapsed/refractory (R/R) settings. Additionally, national claims data from 2023 to 2025 were analyzed in collaboration with Komodo Health to contextualize survey findings and assess alignment with real-world practice.

RESULTS: A total of 101 clinicians responded to the survey (33 academic, 68 community-based). The majority (67%) practice in community-based settings. Most reported routine use of genetic testing: 45% indicating testing prior to initial and subsequent treatments, 40% before first-line therapy only, and 12% only after disease progression. The most frequently used genetic markers included TP53/del(17p) (91%) and IGHV mutation status (78%); 62% use fluorescence in situ hybridization (FISH). Claims data showed variability in molecular testing, FISH, and karyotype analysis use in CLL care.

Treatment strategy preferences were evenly distributed in the survey: fixed-duration regimens were favored by 33% of academic clinicians and 38% of community-based clinicians; TTP regimens were selected by 39% and 40% respectively. However, claims data reflected a stronger preference for TTP: 81% in academic settings and 76% in community settings, with fixed-duration approaches used in just 19% and 24%, respectively.

Venetoclax plus obinutuzumab was the most frequently selected fixed-duration first-line regimen in the survey (72%), a finding corroborated by claims data showing frequent use of obinutuzumab alone (56%) or in combination with venetoclax (42%). In the R/R setting, fixed-duration preferences included venetoclax plus rituximab (39%) and venetoclax plus obinutuzumab (34%). Claims data highlighted venetoclax plus obinutuzumab (53%) and obinutuzumab monotherapy (24%) as top regimens. Key perceived benefits of fixed-duration treatment included finite therapy duration (83%) and reduced treatment burden (77%). Of note chemoimmunotherapy was prescribed in 5% of patients in the frontline setting.

Among TTP strategies, first-line use of acalabrutinib (56%) and zanubrutinib (52%) was prominent in the survey, aligning with claims data that showed both agents as the most prescribed TTP therapies (28% each). In the R/R setting, zanubrutinib (51%) was the most preferred agent among survey respondents. However, claims data diverged, with rituximab (40%) emerging as the most commonly used TTP agent. The main advantages of TTP regimens were prolonged disease control (72%) and suitability for high-risk patients (67%).

CONCLUSIONS: This data highlighted evolving practice patterns in the management of CLL and revealed variation in treatment preferences among academic and community-based clinicians and between survey and claims data. While adoption of genetic testing and newer therapeutic options appears high, clinicians face ongoing challenges in selecting and implementing appropriate regimens, particularly when balancing patient-centered factors with clinical efficacy and operational realities. Both fixed-duration and TTP strategies offer distinct advantages and limitations. These findings emphasize the continued need for targeted education to align clinical decision-making with the latest evidence and to promote personalized, guideline-concordant care in the community setting. Support was provided by an independent educational grant from AstraZeneca Pharmaceuticals.

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2025
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