CALQUENCE® plus venetoclax approved in the US as first all-oral, fixed-duration combination for patients with chronic lymphocytic leukemia in the 1st-line setting
AstraZeneca’sCALQUENCE® in combination with venetoclax has been approved in the US as the first all-oral, fixed-duration regimen for the treatment of adult patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).
The approval by the US Food and Drug Administration (FDA) was based on positive results from the AMPLIFY Phase III trial, which were presented at the American Society of Hematology 2024 Annual Meeting and published in The New England Journal of Medicine.1-2
CLL is the most common type of leukemia in adults.3 An estimated 18,500 people were treated for CLL in the 1st-line setting in the US in 2024.4
Jennifer Brown, MD, PhD, Director of the CLL Center of the Division of Hematologic Malignancies, Dana-Farber Cancer Institute, and the Worthington and Margaret Collette Professor of Medicine at Harvard Medical School, and principal investigator of the AMPLIFY trial, said: “The continuous regimens frequently used to treat chronic lymphocytic leukemia often come with side effects that may become burdensome to patients over time. The US approval of the CALQUENCE combination offers patients an all-oral, 14-month, fixed-duration treatment option that is highly effective and well-tolerated, and gives physicians greater flexibility to tailor treatment plans for individual patient needs and goals.”
Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: Today’s approval delivers the first all-oral, fixed-duration BTK inhibitor-based regimen in the US for the treatment of chronic lymphocytic leukemia. This CALQUENCE combination has the potential to meaningfully change 1st-line chronic lymphocytic leukemia treatment decisions and underscores our commitment to improving on the current standard of care for people living with blood cancers.
Gwen Nichols, MD, Chief Medical Officer of Blood Cancer United, formerly The Leukemia & Lymphoma Society, said: “Managing an incurable blood cancer that progresses slowly can often feel indefinite and overwhelming. We welcome new treatment options that may ease the burden, restore a sense of control and offer renewed hope for those navigating life with chronic lymphocytic leukemia.”
Results from the AMPLIFY Phase III trial showed 77% of patients treated with CALQUENCEplus venetoclax were progression free at three years, versus 67% of patients treated with standard-of-care chemotherapy (investigator’s choice of fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab).2 Median progression-free survival (PFS) was not reached versus 47.6 months for chemoimmunotherapy.2 Further, CALQUENCE plus venetoclax reduced the risk of disease progression or death by 35% compared to chemoimmunotherapy (based on hazard ratio 0.65; 95% confidence interval 0.49-0.87; p=0.0038).2
CALQUENCE plus venetoclax is approved in the European Union, Canada, UK and several other countries, and regulatory applications for the regimen based on the AMPLIFY results are currently under review in additional countries.
Second Primary Malignancies
Second primary malignancies, including skin cancers and other solid tumors, occurred in 16% of 2,055 patients exposed to CALQUENCE in clinical trials. The most frequent second primary malignancy was non-melanoma skin cancer, reported in 9% of patients, followed by other solid tumors in 8% (including melanoma, lung cancer, gastrointestinal cancers, and genitourinary cancers) and hematologic malignancies (1.1%). Fatal second primary malignancies occurred in 0.8% of patients. Monitor patients for the development of second cancers and advise protection from sun exposure.
Cardiac Arrhythmias
Fatal and serious cardiac arrhythmias have occurred in patients treated with CALQUENCE. Grade 3 or 4 atrial fibrillation or flutter was reported in 2.2% of 2,055 patients treated with CALQUENCE, with all grades of atrial fibrillation or flutter reported in 7% of all patients. Grade 3 or higher ventricular arrhythmia events were reported in 0.5% of patients, including fatal cases in 0.3% of all patients. The risk of arrhythmias may be increased in patients with cardiac risk factors, hypertension, previous arrhythmias, and acute infection. Monitor for symptoms of arrhythmia (eg, palpitations, dizziness, syncope, dyspnea) and manage as appropriate.
Hepatotoxicity, Including Drug-Induced Liver Injury
Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of drug-induced liver injury (DILI), has occurred in patients treated with Bruton tyrosine kinase inhibitors, including CALQUENCE.
Evaluate bilirubin and transaminases at baseline and throughout treatment with CALQUENCE. For patients who develop abnormal liver tests after CALQUENCE, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold CALQUENCE. Upon confirmation of DILI, discontinue CALQUENCE.
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