Targeted therapies: Ibrutinib appears superior to idelalisib as first treatment

This study examined the order of treatment with ibrutinib (Imbruvica), idelalisib (Zydelig), and venetoclax (ABT-199) for chronic lymphocytic leukemia (CLL). Researchers concluded that ibrutinib appears superior to idelalisib as first treatment.

Early studies are reporting promising results with targeted therapies for CLL. Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells with less harm to normal cells.

Tyrosine kinase inhibitor therapy is a type of immunotherapy that blocks signals needed for tumors to grow. This includes the Bruton tyrosine kinase inhibitor ibrutinib. Ibrutinib blocks a signal that keeps the CLL cell alive. This treatment is especially helpful in CLL that is hard to treat. Idelalisib is another kinase inhibitor that blocks the protein PI3K. It is often used in patients after other treatments have already been tried. BCL2 inhibitor therapy, such as venetoclax, is a cancer treatment that blocks a protein called BCL2. BCL2 inhibitor therapy kills cancer cells and may make them more sensitive to other anticancer drugs.

Ibrutinib, Idelalisib, and venetoclax have all been approved for the treatment of CLL. The effect of the order of these treatments has not been fully studied.

This study analyzed the records of 683 CLL patients. 91% of patients were treated with ibrutinib first. 9% of patients were treated with idelalisib first. Patients later went on to receive the other kinase inhibitor, venetoclax, or a chemo-immunotherapy combination. The average number of therapies before the study was two. Patients were followed for an average of 17 months.

The overall response rate with ibrutinib as first treatment was 69%. It was 81% with idelalisib as first treatment. The average time until disease progression across all patients was 35 months. Risk of disease progression was significantly reduced with ibrutinib when compared to idelalisib as first treatment. This applied to patients undergoing first-line treatment, those with relapsed disease, and in high-risk patients.

94% of patients discontinued idelalisib and 42% of patients discontinued ibrutinib as first treatment. The most common side effects that led to a discontinuation of ibrutinib included rapid heart rate, infection, lung inflammation, bleeding, and joint pain. For idelalisib, they included lung inflammation, colon inflammation, rash, and infection.

After first kinase inhibitor therapy, the other kinase inhibitor therapy or venetoclax showed better outcomes compared to chemo-immunotherapy. The time to disease progression was significantly improved. After treatment with ibrutinib, patients were more likely to respond to venetoclax than to idelalisib. However, this difference was not statistically significant.

Researchers concluded that ibrutinib appears superior to idelalisib as first treatment. This should be followed by the other kinase inhibitor or venetoclax as opposed to chemo-immunotherapy combinations.

Studies that randomly assign patients to treatment groups are needed to confirm these findings.