First-line treatment with ibrutinib – a review

This study outlined recent evidence on the use of ibrutinib (Imbruvica) for chronic lymphocytic leukemia (CLL).

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, such as when there are certain genetic abnormalities due to CLL or when other treatments have already been tried. The aim of this study was to review evidence on the use of ibrutinib as a first-line treatment.

In an early study involving 269 newly diagnosed CLL patients, ibrutinib was compared to the chemotherapy chlorambucil (Leukeran). At 28.6 months, 41% of patients treated with chlorambucil switched to ibrutinib. 2-year survival was 95% for ibrutinib and 84% for chlorambucil. No significant differences in survival were found for high-risk patients in the ibrutinib group.

45 CLL patients with a genetic abnormality on the TP53 gene received ibrutinib as a first-line treatment. At 2 years, 9% of patients showed disease progression. The 2-year overall survival rate (proportion who have not died from any cause since treatment) was 84%.

Most patients that respond well to treatment will typically undergo a life-time duration of ibrutinib therapy. Long-term use of ibrutinib has been associated with side effects such as diarrhea, discolored skin, joint pain, and fatigue.

Clinical trials that compare first-line ibrutinib to other standards of care are ongoing. This includes a comparison to the chemo-immunotherapy with fludarabine (Fludara), cyclophosphamide (Cytoxan), and rituximab (Rituxan) (also called FCR).

Some patients can progress or stop responding to ibrutinib. In a study involving 17 high-risk CLL patients, 27% progressed at 27 months. Of these, 44% transformed to a more aggressive form of CLL (known as Richter transformation). In a similar study, 5 of 51 patients (9.8%) progressed within 2 years. In a study comparing ibrutinib with ofatumumab (Arzerra), only 4 of 391 patients (1%) developed Richter transformation.

Research is suggesting that combining ibrutinib with other drugs may result in better long-term outcomes. Physically fit patients may receive ibrutinib with FCR as first-line treatment. Of 35 patients, 84% showed no residual leukemia cells after treatment after an average of 104 days. 47% achieved complete remission. No unexpected serious side effects were observed. The benefits of combining ibrutinib with the BCL2 inhibitor therapy venetoclax (Venclexta) is currently being investigated.

Authors concluded that ibrutinib is an effective first-line treatment option for CLL patients, including elderly patients and those with high-risk disease.