Newer CLL Therapies Show Superior Long-Term Disease Control

Second-generation covalent Bruton tyrosine kinase inhibitors (cBTKis) and venetoclax-based regimens offer better long-term disease control and durability compared with older treatments for chronic lymphocytic leukemia (CLL), according to a study published in Cancers.¹

To come to this finding, researchers analyzed electronic health records from 1843 adults in the ConcertAI RWD360 database who were treated for CLL between 2019 and 2023, with a focus on time to next treatment or death (TTNT-D), duration of therapy (DoT), and overall survival. Of these patients, 39.8% received first-generation cBTKis, 23% received second-generation cBTKis, 12.4% received venetoclax-obinutuzumab (VenO), 17.4% received anti-CD20 monotherapy, and 7.4% received chemotherapy/chemoimmunotherapy (CT/CIT).

Venetoclax-based regimens demonstrated the longest TTNT-D at 2 years, with 86.3% of patients not requiring subsequent treatment or experiencing death. Second-generation cBTKis followed closely behind, with 82.5% of patients maintaining disease control over the same period. In contrast, first-generation cBTKis had a TTNT-D of 69.1%, while chemotherapy and anti-CD20 monotherapy had TTNT-D rates of 79.1% and 53%, respectively. These results suggest that more recent therapeutic options may provide better long-term disease management than older regimens.

Researchers analyzed electronic health records from patients in the ConcertAI RWD360 database who were treated for CLL. | Image credit: jarun011 – stock.adobe.com

One of the study’s key observations was that venetoclax-based regimens were used as intended: a fixed-duration therapy rather than continuous treatment. Patients on VenO generally completed their therapy within the expected timeframe, offering a potential benefit in terms of treatment-free intervals. On the other hand, cBTKis, which are designed for continuous administration, were tied to longer treatment durations.

“These findings demonstrate consistency in the real-world setting with prescribing information and demonstrate the rigor of the results reported,” the authors noted.

The authors also highlighted the significance of TTNT-D as a real-world measure of treatment efficacy—in CLL specifically and oncology in general—noting it provides insight into both clinical and patient-centered outcomes.²

“TTNTD shows time to active symptoms requiring further treatment after progression, becoming an important consideration for clinical decision-making,” they said.¹ “Additionally, markers of progression differ between clinicians and between clinical practices, making it difficult to capture reliably in real-world datasets, further highlighting the utility of TTNT-D as an important endpoint.”

Discontinuation rates and the likelihood of switching therapies were also assessed in this study. Among patients initially treated with first-generation cBTKis, nearly half (47%) later transitioned to another cBTKi, while 33% moved to a venetoclax-based regimen. Meanwhile, patients who were first treated with second-generation cBTKis or venetoclax-based therapy were less likely to require additional lines of treatment, suggesting better durability of response.

While real-world data provide valuable insights, the researchers acknowledged certain limitations of their study. For example, treatment selection was not randomized, and patient characteristics varied across treatment groups. Additionally, as electronic health records do not always capture all aspects of treatment adherence or physician intent, some data points may not fully reflect clinical decision-making.

“These findings are notable, as time off treatment affords patients a myriad of benefits, including reduced exposure to side effects, less financial toxicity, fewer disturbances and more conveniences in their daily routine, and fewer mental health/psychosocial effects,” the authors said. “Taken together, these cumulative benefits of a fixed-duration therapy, in contrast to continuous therapy, should be considered in shared decision-making, with the goal of optimizing patient outcomes.”

References

1. Roeker LE, Burke JM, Rhodes JM, et al. Real-world effectiveness of frontline treatments among patients with chronic lymphocytic leukemia: results from ConcertAI. Cancers (Basel). 2025;17(5):799. doi:10.3390/cancers17050799
2. Jacobs R, Lu X, Emond B, et al. Time to next treatment in patients with chronic lymphocytic leukemia initiating first-line ibrutinib or acalabrutinib. Future Oncol. 2024;20(1):39-53. doi:10.2217/fon-2023-0436