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Improved Outcomes Following the Adoption of Targeted Therapies in High-Risk Chronic Lymphocytic Leukemia Treated in Southern Finland

Year: 2025

Type: article

Abstract: BACKGROUND: Targeted therapies have replaced chemoimmunotherapy for chronic lymphocytic leukemia (CLL), but high-risk CLL patients with TP53 aberrations continue to represent a significant unmet medical need. We profiled treatment patterns, outcomes, and adverse effects in a large, unselected cohort of high-risk CLL patients. PATIENTS AND METHODS: This study retrospectively analyzed clinical data from 1,720 CLL patients diagnosed between 2012 and 2023 within the Helsinki University Hospital district in Southern Finland. We focused on 543 patients who received first-line (1 L) systemic treatment. RESULTS: Of the 543 treated patients, 78 (14.4%) had a TP53 aberrations. A clear shift in treatment patterns occurred after 2018, with targeted therapies comprising over one-third of 1 L regimens. For high-risk patients, ibrutinib use at the 1 L stage rose dramatically after 2018, replacing chemoimmunotherapy as the most common treatment. This change coincided with a marked increase in the median time-to-next-treatment (TTNT) for high-risk patients, from 21.2 months (2012-2017) to 26.0 months (2018-2023). Increased TP53 and IGHV mutation testing rates facilitated more personalized treatment approaches over time. Adverse events were less frequent in patients receiving targeted therapies (62.1%) compared to those on non-targeted regimens (73.5%). Despite these improvements, the median overall survival (OS) for high-risk patients remained challenging at 47.1 months after 1 L treatment. CONCLUSION: The transition to targeted therapies has improved outcomes for high-risk CLL patients. Nevertheless, outcomes for high-risk CLL patients remain inferior to those reported in clinical trials, underscoring the need for real-world evidence and improved therapies.

Source: Clinical Lymphoma Myeloma & Leukemia

DOI: 10.1016/j.clml.2025.12.002