In a nutshell
This study examined venetoclax (Venclexta) for patients with chronic lymphocytic leukemia (CLL) previously treated with idelalisib (Zydelig). Researchers reported good response rates and a low rate of side effects for venetoclax after idelalisib.
Targeted therapy is the standard treatment of CLL. This includes the tyrosine kinase inhibitor idelalisib. Idelalisib blocks the protein PI3K that keeps the CLL cell alive. Many patients achieve complete remission (no sign of active disease) with idelalisib therapy. However, some patients stop responding to idelalisib (refractory) or relapse after therapy. These patients can be difficult to treat. Relapse is observed more often in high-risk patients such as those with certain genetic abnormalities due to CLL.
BCL2 inhibitor therapy with venetoclax has recently been approved for relapsed or refractory CLL. It may be suitable for patients previously treated with idelalisib.
Methods & findings
36 patients with relapsed or refractory CLL were included in this study. All patients were previously treated with idelalisib (for an average of 9 months). The average number of previous therapies was 3. Most patients had at least one high-risk feature, such as the genetic abnormalities known as del(17p) and TP53 mutation. All patients received venetoclax for an average of 14 months.
The overall response rate for all patients was 67%. 3 patients (8%) achieved complete remission. 21 patients (58%) achieved partial response. The average time to treatment response was 2.5 months. At 12 months, 79% of patients were estimated to be progression-free. The estimated overall survival rate (proportion who have not died from any cause since treatment) at 12 months was 94%.
For the 13 patients who stopped idelalisib due to disease progression, the overall response rate was 46%. For the 22 patients who stopped idelalisib due to side effects, the overall response rate was 82%.
The most common serious side effects involved low red and white blood cell counts. Side effects not related to blood results included diarrhea (42%), chest infection (39%), nausea (31%), fatigue (28%), cough (22%), and rash (22%). No treatment-related deaths were reported.
The bottom line
This study concluded that venetoclax was associated with a high overall response rate in patients with relapsed or refractory CLL after idelalisib.
The fine print
This was an early-phase study on a small number of patients. Larger studies are needed to confirm these findings.
Published By :
Jan 05, 2018