Defining and managing high-risk CLL has evolved in recent years with availability of novel therapies. In this segment of the CLL Discussion series CARE™ Hematology Faculty members Dr. Peter Anglin (Stronach Regional Cancer Centre) and Barbara Eichhorst (University Hospital Cologne) discuss best practices for managing high-risk patients in light of recent data and advances.
What factors do you use to define the high-risk patient?
- Most prominent risk factor (for the last 20 years) is 17p deletion (del17p)
- TP53 mutations (12-15% of Front Line patients who have this mutation on both alleles can be considered very high-risk).
- Complex karyotypes – patients who have 5 different chromosomal aberrations (even without del17p) can be considered high risk.
- 11q is no longer considered high risk with availability of novel targeted agents.
- Knowing IGVH mutation status can help direct choice of therapy (i.e. BTKi vs. BCL-2)
What is your approach for treating del17p patients in the front-line setting?
- Currently, continuous treatment (with BTKi) is recommended.
What recent data in this population has impacted how you treat?
- Newer BTKi’s have promising data in del17p patients
- early read out of APLINE trial of zanubrutinib, EHA 2021
- Non-covalently binding BTKi’s (i.e. Pirtobrutinib)
What about testing and treatment of asymptomatic patients?
- Data is emerging to suggest that early treatment with a BTKi in these patients can result in better outcomes (EFS, OS data anticipated)
Where in the new world with novel agents does transplant fit in your practice for high-risk patients?
- In more patients (especially those younger and fitter) we are using transplant in later lines given the impressive efficacy of novel agents and possibility to reduce morbidity associated with the allo transplant procedure. ‘
Final comments on high-risk CLL
- It is important to do what we can to try and avoid patients becoming double-refractory.
- If a patient develops toxicity to their treatment, do not change your approach too early. Consider dose reduction or interruption, or switching to another agents in the same class.