Evaluating the combination of obinutuzumab, ibrutinib and venetoclax in chronic lymphocytic leukemia

This study aimed to investigate the safety and effectiveness of the combination of obinutuzumab (Gazyva), ibrutinib (Imbruvica) and venetoclax (Venclexta) in patients with chronic lymphocytic leukemia. 

This study concluded that this treatment is safe and effective for these patients.  

Highly effective targeted therapies have been developed for chronic lymphocytic leukemia (CLL). These therapies offer the potential for fixed-duration combinations that achieve deep remission without cytotoxic (toxic to healthy cells) chemotherapy. 

Obinutuzumab, ibrutinib and venetoclax are targeted therapies that have been used alone or combine with chemotherapy in patients with CLL. However, the effectiveness and safety of the combination of obinutuzumab, ibrutinib and venetoclax in CLL patients remain under investigation.

This study involved 50 patients with CLL. 25 patients had never been treated before (treatment naive; TN group) and 25 patients were relapsed or refractory to treatment (RR group). Patients were treated with a combination of obinutuzumab, ibrutinib, and venetoclax for a total of 14 cycles. Patients were followed up for an average of 21.5 months (RR group) to 24.2 months (TN group).

At the end of treatment, 84% of patients in the TN group and 88% in the RR group responded to treatment. 2 months after the end of treatment, the rate of complete remission with undetectable minimal residual disease (MRD – no signs of cancer) was 28% for both the TN and RR groups.   

After 24.2 months in TN group, the progression free survival (PFS) and overall survival (OS) were not yet reached. After 21.5 months in the RR group, the PFS and OS were not yet reached. At this time, 1 patient experienced disease progression and there was 1 death.  

The most frequent side effects were neutropenia (94%; low level of white blood cells) and thrombocytopenia (90%; low level of platelets). Hypertension (high blood pressure) was also a common AE. 66% of patients experienced grade 3 or 4 neutropenia. 6% of patients stopped treatment due to side effects.

This study concluded that the combination regimen of obinutuzumab, ibrutinib, and venetoclax for CLL offers time-limited treatment that results in deep remissions. 

This was a small phase 2 trial. A phase 3 trial is still ongoing. This trial was funded by the manufacturers of obinutuzumab, ibrutinib, and venetoclax.