Brukinsa Recommended Versus Imbruvica in R/R CLL, SLL

Treatment with BTK inhibitor Brukinsa (zanubrutinib) demonstrated superior effectiveness compared with BTK inhibitor Imbruvica (ibrutinib) in patients with relapsed (disease worsening after a period of improvement) or refractory (resistant to treatment) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to a study.

A BTK inhibitor is a type of drug that blocks the activity of the Bruton tyrosine kinase protein, which is key in the development of B cells. These cells are a type of white blood cells that make antibodies, a special type of protein. The drug binds to BTK proteins to potentially stop the growth of cancer cells, according to the National Cancer Institute.

Before BTK inhibitors like Brukinsa and Imbruvica, patients with CLL or SLL received chemotherapy. However, “for some time now, BTK inhibitors like [Brukinsa] and [Imbruvica] have come into play. Patients can also get venetoclax-based therapy,” explained study author Dr. Jennifer R. Brown in an email interview with CURE®.

Brown is a medical oncologist and director of the CLL Center of the Division of Hematologic Malignancies at Dana-Farber Cancer Institute and the Worthington and Margaret Collette Professor of Medicine at Harvard Medical School, both in Boston.

Of note, a study published in the journal Blood demonstrated that patients who received Brukinsa had more favorable cardiac (heart) safety and tolerability versus Imbruvica. Because of the superior effectiveness of Brukinsa versus Imbruvica for longer than three years, the researchers emphasized that “we felt it was not in the best interest of patients to continue [Imbruvica].”

“As such, a decision was made to close the [ALPINE] study and allow eligible patients, including those originally assigned to [Imbruvica], to enroll in LTE-1,” the researchers wrote.

ALPINE was a phase 3 trial that included 652 patients who were randomly assigned to two groups: Brukinsa or Imbruvica. There were 327 patients in the Brukinsa group and 325 patients in the Imbruvica group, the researchers noted. In the Brukinsa and Imbruvica groups, the median follow-ups were 43.4 months and 41.6 months, respectively.

At an overall median follow-up of 42.5 months, the progression-free survival (PFS; time patients live without experiencing disease worsening or spreading) benefit was sustained in patients who received Brukinsa versus Imbruvica.

“I think one of the most interesting findings is that the benefit of [Brukinsa] is even greater in the highest risk subgroup of patients, those with 17p deletions,” Brown said.

Regarding the overall response rate (ORR; percentage of patients whose tumors shrunk or disappeared after treatment), patients treated with Brukinsa had a higher ORR at the overall follow-up of 42.5 months. The rate of partial responses with lymphocytosis (increase in lymphocytes, a type of infection-fighting white blood cell) or better was 90.2% compared with 82.8% in patients receiving Brukinsa and Imbruvica, respectively.

Side Effects Associated With Brukinsa and Imbruvica

The majority of side effects year after year remained stable, the study stated. Common changes included changes in neutropenia (lower levels of neutrophils, a type of white blood cell) and anemia reported in patients over time.

The majority of COVID-19-related infections were also reported between 24 and 36 months, according to the study. Reported deaths related to COVID-19 infection included 21 in the Brukinsa group and 22 in the Imbruvica group.

Other common treatment-emergent non-blood-related side effects in the Brukinsa and Imbruvica groups included upper respiratory tract infection, diarrhea and hypertension. Neutropenia was the most common blood-related side effect of any severity, the researchers explained.

“[Brukinsa] is a great treatment option, very well tolerated and highly effective. [Brukinsa] showed much reduced cardiac side effects compared to [Imbruvica] — this is something patients are often worried about,” Brown said.

In terms of ways patients can help manage their side effects, Brown noted thatthere is “not that much, just the usual: eat right, get enough sleep, manage stress and exercise.”

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