At the ASH 2022 annual meeting, Dr. Meghan Thompson, a CLL expert from Memorial Sloan Kettering Cancer Center in New York, expressed there is an unmet need for high-risk CLL patients that have tried covalent BTK inhibitors followed by any non-covalent BTK inhibitors and have become resistant to treatment. Data gathered from treated patients in her clinic and data from clinical trials suggests a venetoclax regimen (if the patient has not yet been treated with venetoclax) or cellular-based therapies like CAR T-cell or allogeneic stem cell transplants have a high overall response rate (ORR) meaning the % of patients in which the cancer was significantly reduced. 

Watch the Full Video with Meghan Thompson, MD Here:

Non-Covalent BTK Inhibitors May Increase BTK Mutations and Treatment Resistance for CLL Patients 

The data also showed that prior to non-covalent BTK inhibitor treatment, 38.5% of the CLL patients started with the BTKC481 mutation and 33% had the PLCG2 mutation. After non-covalent BTK inhibitor treatment, 73% of the patients developed a new BTK mutation (BTKL528W, BTKV416L, and/or BTKT474I), and the PLCG2 mutation persisted leading to increased treatment resistance.

Treatment Type and ORR for CLL Patients Resistant to Non-Covalent BTK Inhibitors

Higher ORR (more favorable outcomes) 

• Venetoclax-based therapy: 70% 
• Cellular therapies:
  • NK CAR T-cell therapy: 100%
  • CD19-directed CAR T-cell therapy: 85.7% 
  • Allogenic stem cell transplant: 83.3% 

Lower ORR (not recommended) 

• Alternative covalent BTK inhibitor: 66.7% 
• Chemo or chemoimmunotherapy: 18.8% 
• Anti-CD20 antibody monotherapy (used by itself and not in a combination treatment): 0% 
• Alternative non-covalent BTK inhibitor: 0% 
• PI3 kinase inhibitor: 0% 

CLL patients with resistance to non-covalent BTK inhibitors are encouraged to enroll in clinical trials such as CAR T-cell therapy to help advance treatment options. 

For more information about CAR T-cell therapy and joining CAR T-cell clinical trials, see here: What is CAR T-cell Therapy?