EU committee recommends fixed-duration Calquence combo for CLL
Treatment reduced risk of blood cancer progression in Phase 3 trial
A European regulatory committee has recommended approval of a fixed-duration regimen of AstraZeneca’s Calquence (acalabrutinib) for adults with previously untreated chronic lymphocytic leukemia (CLL), a type of blood cancer.
The recommendation, from the Committee for Medicinal Products for Human Use, known as CHMP, covers Calquence combined with venetoclax (sold as Venclyxto in Europe and Venclexta in the U.S.), another CLL therapy. Gazyva (obinutuzumab), which is also used for CLL, may accompany the regimen. In the Phase 3 AMPLIFY clinical trial (NCT03836261), treatment with one of these Calquence combinations was found to reduce the risk of CLL progression.
The European Commission, which is in charge of final therapy approvals in the EU, will review CHMP’s recommendation. While not binding, the European Commission generally follows CHMP’s recommendations.
This fixed-duration regimen differs from a treat-to-progression strategy, in which patients receive the therapy until their disease progresses. U.S. and European Union regulatory bodies have already approved treat-to-progression Calquence for CLL. However, that model may pose some disadvantages, according to Wojciech Jurczak, MD, an investigator from the AMPLIFY trial.
“Chronic lymphocytic leukaemia is an incurable cancer which means patients live with the disease and stay on treatment for many years, which can have long-term effects,” Jurczak said in an AstraZeneca press release. “The fixed-duration Calquence regimens will allow patients to take breaks from their treatment, reducing the risk of long-term adverse events and drug resistance.”
European Commission now to decide on Calquence approval for CLL
This new treatment regimen is under review in several other countries as well, per the press release. Earlier this year, Calquence was also approved in the U.S. for mantle cell lymphoma, a rare blood cancer.
CLL occurs when immune cells called B-cells experience uncontrolled growth. Calquence and venetoclax both target proteins involved in B-cell function and survival. While Calquence inhibits Bruton’s tyrosine kinase (BTK), a signaling protein involved in B-cell function, venetoclax blocks a protein that helps the cancerous B-cells survive.
Susan Galbraith, PhD, AstraZeneca’s executive vice president of oncology hematology research and development, noted that, “with this recommendation, Calquence plus venetoclax can potentially be the only all-oral second-generation BTK inhibitor option approved in Europe for patients with previously untreated chronic lymphocytic leukaemia.”
Results from the AMPLIFY trial played into CHMP’s recommendation. Those findings showed that Calquence plus venetoclax reduced the risk of disease progression in CLL compared with chemoimmunotherapy, a standard treatment approach.
Calquence has demonstrated efficacy and safety in fixed-duration and treat-to-progression regimens providing patients and their doctors more treatment flexibility.
In the study, two groups of leukemia patients received twice-daily doses of Calquence for 14 treatment cycles lasting 28 days each. Starting in the third cycle, the participants also received venetoclax once a day. Participants in one of these groups received additional intravenous, or into-the-vein, injections of obinutuzumab during cycles two through seven.
Compared with the chemoimmunotherapy group, the combination without obinutuzumab reduced the risk of disease progression or death by 35%. With obinutuzumab, this risk was reduced by 58%, the data showed.
After three years, the cancer had not progressed in 77% of those treated with Calquence plus venetoclax, and in 83% of those with added obinutuzumab. This compared favorably to the 67% of the control group patients whose disease did not progress during this time.
AMPLIFY did not identify any new safety concerns related to Calquence. Serious adverse events occurred in 24.7% to 38.4% of participants across the three groups. Infections and neutropenia —low counts of neutrophils, a type of immune cell — were the most common adverse events resulting in treatment interruption.
“Calquence has demonstrated efficacy and safety in fixed-duration and treat-to-progression regimens providing patients and their doctors more treatment flexibility,” Galbraith said.
According to AstraZeneca, there were an estimated 27,000 people diagnosed with CLL in 2024 across France, Germany, Italy, Spain, and the U.K.
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