Dr Allan on Efforts to Clarify the Optimal Treatment Sequence in CLL

John N. Allan, MD, associate professor, clinical medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, discusses ongoing efforts to address lingering areas of uncertainty regarding the optimal sequencing strategy for patients with chronic lymphocytic leukemia (CLL), as highlighted in his presentation at the 42nd Chemotherapy Foundation Symposium (CFS) Symposium PER®, on the existing knowledge gap in determining optimal sequencing strategies for patients with chronic lymphocytic leukemia (CLL). on the existing knowledge gap in determining optimal sequencing strategies for patients with chronic lymphocytic leukemia (CLL).

Despite advances in the treatment paradigm, there remains no universally accepted standard sequence of treatment in CLL. Currently, the treatment armamentarium in CLL includes BTK inhibitors, BCL-2 inhibitors, and, in some cases, chemoimmunotherapy. However, no definitive evidence supports the superiority of one sequencing approach over another.

This lack of consensus stems from limited prospective data comparing sequencing strategies across different patient populations. This leaves clinicians to rely on retrospective analyses and real-world evidence to inform treatment selection, Allen explains.

Allan emphasizes the critical need to address knowledge gaps in sequencing for patient populations with less aggressive disease or no prior exposure to chemoimmunotherapy, as the majority of available data on sequencing strategies are derived from studies involving patients with high-risk features, such as relapsed or refractory disease, or those who have previously received chemoimmunotherapy.

It is unclear whether favorable outcomes with select treatment approaches that are observed in these higher-risk populations will translate to treatment-naive or lower-risk patient populations. Patients without prior chemoimmunotherapy exposure may experience even better outcomes, but this supposition requires validation in prospective clinical trials.

Additionally, there is uncertainty regarding the long-term effects of sequencing decisions on progression-free survival, overall survival, and the durability of responses in various patient subsets.

Allan concludes that further research is essential to validate sequencing strategies in CLL . Ongoing studies should focus on evaluating chemoimmunotherapy-naive or low-risk patient populations to determine whether outcomes align with or improve upon those reported in higher-risk cohorts. This information could better inform decision-making in CLL, ultimately leading to improved outcomes for patients with CLL, Allan concludes.