Calquence-Based CLL Regimen May Improve Survival

A treatment combination of Calquence (acalabrutinib) plus Venclexta (venetoclax) with or without Gazyva (obinutuzumab) in the first-line setting significantly improved progression-free survival (PFS) in patients with chronic lymphocytic leukemia (CLL) who were previously untreated.

Of note, PFS is the length of time patients live without their disease worsening or spreading.

Calquence is an inhibitor that blocks Bruton tyrosine kinase (BTK), a protein found on most B cells and certain types of cancer cells, as defined by the National Cancer Institute. By inhibiting this protein, the drug can effectively help prevent the cancer from growing.

The phase 3 AMPLIFY trial included 984 patients with CLL who were previously untreated, according to a news release from AstraZeneca, the manufacturer of Calquence. Patients were randomly assigned evenly among three treatment groups:

• Calquence plus Venclexta
• Calquence plus Venclexta and Gazyva
• Standard-of-care chemoimmunotherapy

Patients who received Calquence plus Venclexa with or without Gazyva demonstrated better PFS, compared with patients in the chemoimmunotherapy groups, researchers found. Specific statistics on PFS were not revealed in the news release.

“The AMPLIFY results demonstrate the potential of [Calquence] and [Venclexta] with or without [Gazyva] to be effective and well-tolerated fixed-duration treatment options for patients with chronic lymphocytic leukemia,” Dr. Jennifer R. Brown said in the news release. “This is an important advance in this setting as fixed-duration regimens allow those living with this chronic disease to take breaks from their treatment, thereby decreasing the possibility of long-term adverse events and drug resistance and improving quality of life.”

Brown is the director of the CLL Center of the Division of Hematologic Malignancies, professor of medicine at Worthington and Margaret Collette at Harvard Medical School, and principal investigator of the AMPLIFY trial.

The secondary endpoint (an objective measured at the end of a study to see if treatment worked) of the trial was overall survival (OS; time patients live, regardless of their disease status), according to the release. Researchers found that there was also a trend in favor for Calquence plus Venclexta with or without Gazyva regarding OS when compared with chemoimmunotherapy.

These OS data were not mature at the time of the analysis, meaning not enough patients in the trial died for the researchers to calculate an average time to death. OS will continue to be analyzed as a secondary endpoint, the release stated.

“The [PFS] and overall survival results from the AMPLIFY phase 3 trial demonstrate the potential of including a BTK inhibitor in a fixed-duration regimen and reinforce our leadership in advancing science for patients with [CLL],” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, said in the release.

Researchers reported that the safety and tolerability were consistent for each of the drugs given during the trial. No new safety signals were found, although lower rates of cardiac toxicity were observed, the release stated. Specific data from the trial will be presented at an upcoming scientific meeting.

The trial began in February 2019 and is expected to be completed in January 2027, according to AstraZeneca’s trial listing.

“If approved, Calquence would become the only second-generation BTK inhibitor available as both a treat-to-progression and fixed-duration treatment, providing more options for patients and their health care providers,” Galbraith said in the release.

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