Is entospletinib an effective treatment for relapsed or unresponsive chronic lymphocytic leukemia?

This study examined if entospletinib can be used as a treatment for relapsed or unresponsive chronic lymphocytic leukemia (CLL). This study concluded entospletinib has disease reducing activity in patients with CLL, where previous treatment has failed.

Chronic lymphocytic leukemia (CLL) is a cancer of the bone marrow. It is often seen in older patients and is associated with abnormal genes. It can lead to abnormal cells of the immune system. Richter’s transformation (RT) can happen if CLL does not respond to treatment, and progresses. This is an aggressive form of cancer associated with poorer outcomes.

B-cell receptor (BCR) inhibitors are currently used to treat some types of CLL. These work by blocking a protein that promotes cancer cell survival. This leads to cancer cell death. Sometimes, this treatment is not effective, and other treatment options must be investigated. Entospletinib is an experimental drug. It is thought to act as a tyrosine kinase inhibitor (TKI). TKIs are drugs which target certain abnormal proteins on cancer cells.

It is not known if entospletinib is an effective treatment for unresponsive or relapsed CLL.

49 patients with relapsed or unresponsive chronic lymphocytic leukemia (CLL) were included in this study. They received entospletinib. 8 of these patients had RT. All patients had received previous treatment with a BCR inhibitor.

16 patients had a partial response (tumor shrinkage) to treatment. In 21 patients, the disease was stable and had not gotten worse. 21 patients also had a decrease in the size of cancer in the lymph nodes. Overall, 32.7% of patients had a response to treatment. The average length of survival before cancer progressed was 5.6 months. 

All patients on this trial experienced side effects. The most common were fatigue (25%), diarrhea (31%), and low levels of iron in the blood (14%). Infections occurred in 65% of patients (12% of these were serious).

76% of patients discontinued the study. This was due to the progression of disease in 41% of patients. The other common reasons for discontinuing the study included side effects (12%), and on doctors advice (10%). 

Five patients died within 30 days of the last entospletinib dose. Four of these were due to progression of the disease, and one due to a cardiac arrest.  

This study concluded that entospletinib has disease reducing activity in patients with CLL, where previous treatment has failed.

This study was funded by Gilead Sciences, the makers of entospletinib.

This was a small Phase 2 study. Further studies are needed to determine the role of entospletinib in the treatment of relapsed or unresponsive CLL.