ASH 2023: Updates from the CLL2-BAAG Trial

CLL expert Dr. Moritz Fürstenau from the University of Cologne in Koeln, Germany shared updates about phase 2 of the CLL2-BAAG trial at the recent ASH conference. In phase 2 of a clinical trial, doctors are reviewing how safe a therapy is and how well it works for patients. The CLL2-BAAG study analyzed a new treatment combination for patients with relapsed/refractory CLL.

The study tested a triplet combination therapy of BTK inhibitor acalabrutinib (Calquence), BCL-2 inhibitor venetoclax (Venclexta), and monoclonal antibody obinutuzumab (Gazyva) over a fixed-duration or defined period of time. The study’s goal was to evaluate minimal residual disease (MRD) following treatment. 

What is MRD and How is it Tested?  

“Minimal residual disease (MRD) in CLL is defined as the number of leukemic cells that can be detected in peripheral blood or bone marrow following treatment. Undetectable MRD (uMRD) is currently defined as the presence of less than 1 CLL cell in 10,000 leukocytes.” (National Library of Medicine). 

MRD testing helps find the smallest number of cancer cells that may remain in a patient's body following treatment, or during remission periods. Its sensitivity is so high that it can identify remaining cancer cells that often go undetected by conventional clinical or laboratory tests. This detection ability helps give healthcare professionals highly accurate insight into the depth of a patient's response to treatment.

The types of MRD testing used in the CLL2-BAAG study were flow cytometry and polymerase chain reaction (PCR). Samples of patients’ blood were used to conduct the MRD testing. The researchers found that PCR detected MRD occurrence first more often than flow cytometry. PCR detected MRD occurrence in samples first 65% of the time whereas flow cytometry detected MRD occurrence first 35% of the time. They also found that PCR testing helped detect relapse earlier than flow cytometry. PCR detected relapse 8 months earlier than flow cytometry. 

More About the Study 

Patients received a combination of the medicines at different intervals during 6 cycles (each cycle was 28 days). Further administration of treatment using a combination of the medicines was given for an additional up to 8 cycles if the CLL persisted and the patient did not achieve uMRD. 

Study Participants 

• 45 relapsed/refractory CLL patients 
• 40% of the patients had received a prior BTK inhibitor and/or venetoclax
• 31.8% of the patient group had del(17p)/TP53 mutation 
• 75.6% of the patients had unmutated IGHV 

Study Results 

• 75.6% of patients achieved uMRD after the first 6 cycles and stopped treatment 
• The remaining patients who did not achieve uMRD after the 6 cycles went on to receive additional treatment cycles. 70% of these patients achieved uMRD at some point during the following 8 treatment cycles
• 4% of patients still had detectable MRD after 8 cycles of maintenance therapy 

CLL had not progressed (progression-free survival) at the check-in point of 30 months for:

• 88.2% of the total patient group 
• 85.7% of patients with del(17p)/TP53 mutation
• 93.3% of patients that had previously been treated with venetoclax and/or a BTK inhibitor 

Side Effects

Serious side effects that some patients experienced during this treatment included: 

• COVID-19 (17% patients) 
• Pneumonias (11% patients) 
• Infusion-related reactions (11% patients) 
• Neutropenias (6% patients)
• Only 4% of the patients stopped treatment because of side effects 

See here for how CLL specialists help manage the side effects of treatment for patients.

Conclusion

The CLL2-BAAG study evaluated treating relapsed/refractory CLL patients with a combination of acalabrutinib, venetoclax, and obinutuzumab over a fixed period of time. Its findings showed promising evidence of an effective treatment combination for high-risk and previously treated CLL patients with manageable side effects. The study showed evidence of a long lasting period of the disease not progressing following treatment. We look forward to continued advancements in the treatment landscape for CLL patients.

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