Evaluating the long-term effectiveness and safety of fixed-duration combination of ibrutinib plus obinutuzumab-based immunochemotherapy for patients with chronic lymphocytic leukemia.

This study reported the long-term effectiveness and safety of the fixed-duration combination of ibrutinib (Imbruvica) plus obinutuzumab (Gazyva)–based immunochemotherapy for patients with previously untreated chronic lymphocytic leukemia (CLL). The data showed that a fixed-duration combination of ibrutinib plus obinutuzumab-based immunochemotherapy was safe and effective for these patients.

CLL is a type of cancer that affects the blood and bone marrow. Chemoimmunotherapy (CIT) combines chemotherapy (CT) with immunotherapy (IT). CT uses drugs to kill or slow the growth of cancer cells. IT uses treatments to stimulate the immune system or restore its ability to fight cancer. Combined, fludarabine (Fludara), cyclophosphamide (Cytoxan), and rituximab (Rituxan) have been an effective treatment for patients with CLL. This regimen has been shown to work particularly well in patients who have an abnormal IGHV gene.

Highly effective targeted therapies have been developed for CLL. These therapies offer the potential for fixed-duration combinations that achieve deep remission without cytotoxic (toxic to healthy cells) chemotherapy. Obinutuzumab and ibrutinib are targeted therapies that work by blocking the growth of cancer cells. Both targeted therapies are commonly used in the treatment of CLL and improve survival in the short-term. These treatments can be taken alone or combined with other chemotherapy. However, the long-term effectiveness and safety of a fixed-duration combination of ibrutinib plus obinutuzumab-based CIT for patients with previously untreated CLL are still unknown.

This study involved 135 patients with CLL who received obinutuzumab and ibrutinib induction (for reducing tumor before other treatment; lead-in treatment) for 9 months. Patients were tested for minimal residual disease (MRD) response rate and assigned into 2 groups. MRD is the small number of cancer cells that remain after treatment. The treatment goal was undetectable MRD. Group 1 included 10 patients who had confirmed undetectable MRD (less than 0.01%) and received ibrutinib alone for 6 more months. Group 2 included 125 patients who did not have confirmed undetectable MRD and received ibrutinib plus obinutuzumab, fludabarine, and cyclophosphamide combination. The average follow-up time was 63 months.

At month 40, 92.5% of all patients achieved an undetectable MRD response rate (less than 0.01%) in the blood. At month 64, 80.6% of all patients achieved an undetectable MRD response rate (less than 0.01%) in the blood.

After 4 years, 96.2% of all the patients were alive and 95.5% of all the patients were alive without progression or cancer worsening. After 5 years, 93.6% of all the patients were alive and 92.8% of all the patients were alive without progression or cancer worsening.

There were a total of 14 serious side effects which occurred after the end of treatment.

This study concluded that a fixed-duration combination of ibrutinib plus obinutuzumab-based immunochemotherapy was safe and effective for the treatment of patients with previously untreated CLL.

This study was funded by Roche and Janssen Pharmaceuticals, the manufacturers of obinutuzumab and ibrutinib.