Evaluating the effectiveness and safety of fixed-duration treatment with ibrutinib plus venetoclax for patients with chronic lymphocytic leukemia.

This study investigated the effectiveness and safety of fixed-duration treatment with ibrutinib (Imbruvica) plus venetoclax (Venclexta) for patients with previously untreated chronic lymphocytic leukemia (CLL) by using minimal residual disease (MRD) guidance. The data showed that fixed-duration treatment with ibrutinib plus venetoclax was safe and effective for these patients.

CLL is a type of cancer that affects the blood and bone marrow. Ibrutinib and venetoclax 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. However, when taken alone only a few patients achieve undetectable minimal residual disease (MRD) response rates and need to be taken indefinitely. MRD is the small number of cancer cells that remain after treatment. The treatment goal is undetectable MRD.

Recent studies have shown that combining ibrutinib and venetoclax demonstrated high undetectable MRD response rates in both blood and bone marrow in patients with CLL. However, the effectiveness and safety of fixed-duration treatment with ibrutinib plus venetoclax for patients with previously untreated CLL by using MRD guidance are still unknown.

This study involved 149 patients with CLL who received 3 cycles of ibrutinib (for reducing tumor before other treatment; lead-in treatment) followed by 12 cycles of combined ibrutinib plus venetoclax. Patients were tested for MRD response rate and randomly assigned into 2 groups. Group 1 included 86 patients who had confirmed undetectable MRD and were randomly assigned to receive either ibrutinib (43) or placebo (43). Group 2 included 63 patients who did not have confirmed undetectable MRD and were randomly assigned to receive either ibrutinib (31) or ibrutinib plus venetoclax (32). The average follow-up time was 31.3 months.

After the ibrutinib lead-in, 90% of the patients whose risk for tumor lysis syndrome (TLS) was high at the beginning of the study shifted to medium or low risk. TLS occurs when a large number of cancer cells are killed at once and their byproducts enter the bloodstream. If left untreated, TLS can lead to acute kidney failure, heart rate problems, neurological complications, and seizures.

Overall, 75% of patients achieved an undetectable MRD response rate in the blood and 72% in the bone marrow. In group 1, all (100%) patients achieved undetectable MRD response rates in both the blood and bone marrow. In group 2, 57% of patients achieved an undetectable MRD response rate in the blood and 54% in the bone marrow after treatment.

After 1 year, 100% of the patients in group 1 who received ibrutinib were alive without any signs of cancer compared to 95% of patients who received placebo. This difference was not significant.

After 30 months, 100% of the patients in group 1 who received ibrutinib were alive without progression or cancer worsening compared to 95% of patients who received placebo. In group 2, 97% of the patients who received ibrutinib plus venetoclax were alive without progression or cancer worsening compared to 95% of patients who received ibrutinib.

Side effects were more common in patients treated with ibrutinib plus venetoclax. The most common side effects were low white blood cell counts, high blood pressure, low platelet cell counts, and diarrhea.

This study concluded that fixed duration treatment with ibrutinib plus venetoclax was safe and effective for the treatment of patients with previously untreated CLL.

This study was funded by Janssen Pharmaceuticals and Pharmacyclics, the manufacturers of ibrutinib and venetoclax.