お知らせ • Feb 20
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’s CALQUENCE (acalabrutinib) 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. CLL is the most common type of leukemia in adults. An estimated 18,500 people were treated for CLL in the 1st-line setting in the US in 2024. Serious and Opportunistic InfectionsFatal and serious infections, including opportunistic infections, have occurred in patients with hematologic malignancies treated with CALQUENCE. Serious or Grade 3 or higher infections (bacterial, viral, or fungal) occurred in 29% of 2,055 patients exposed to CALQUENCE in clinical trials, most often due to respiratory tract infections (18% of all patients, including pneumonia in 14%). These infections predominantly occurred in the absence of Grade 3 or 4 neutropenia, with neutropenic infection reported in 8% of all patients. Opportunistic infections in recipients of CALQUENCE have included, but are not limited to, hepatitis B virus reactivation, fungal pneumonia, Pneumocystis jirovecii pneumonia, Epstein-Barr virus reactivation, cytomegalovirus, and progressive multifocal leukoencephalopathy (PML). Consider prophylaxis in patients who are at increased risk for opportunistic infections. Monitor patients for signs and symptoms of infection and treat promptly. HemorrhageFatal and serious hemorrhagic events have occurred in patients treated with CALQUENCE. Major hemorrhage (serious or Grade 3 or higher bleeding or any central nervous system bleeding) occurred in 4.7% of patients, with fatal hemorrhage occurring in 0.1% of 2,055 patients exposed to CALQUENCE in clinical trials. Bleeding events of any grade, excluding bruising and petechiae, occurred in 39% of patients. Use of antithrombotic agents concomitantly with CALQUENCE may further increase the risk of hemorrhage. In clinical trials, major hemorrhage occurred in 5% of patients taking CALQUENCE without antithrombotic agents and 3.2% of patients taking CALQUENCE with antithrombotic agents. Consider the risks and benefits of antithrombotic agents when co-administered with CALQUENCE. Monitor patients for signs of bleeding. Consider the benefit-risk of withholding CALQUENCE for 3 to 7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding. CytopeniasCALQUENCE can cause Grade 3 or 4 cytopenias. Grade 3 or 4 cytopenias included absolute neutrophil count decreased (28%), absolute lymphocyte count decreased (10%), hemoglobin decreased (9%), and platelets decreased (9%) in 1,758 patients treated with CALQUENCE alone and in combination with obinutuzumab or venetoclax; Grade 4 neutropenia developed in 14% of patients. Monitor complete blood counts regularly during treatment. Interrupt treatment, reduce the dose, or discontinue treatment as warranted. Second Primary MalignanciesSecond 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 ArrhythmiasFatal 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 InjuryHepatotoxicity, 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. ADVERSE REACTIONSChronic Lymphocytic Leukemia
In patients with previously untreated CLL in the AMPLIFY study who received CALQUENCE plus venetoclax (AV) (n=291), the most common adverse reactions (=15%) of any grade were headache (35%), diarrhea (33%), musculoskeletal pain (25%), COVID-19 (21%), fatigue (18%), bruising (17%), rash (16%), and nausea (15%). The most common laboratory abnormalities (=15%) of any grade in patients with previously untreated CLL who received AV were neutrophils decreased (78%), glucose increased (74%), lymphocytes decreased (56%), platelets decreased (43%), hemoglobin decreased (35%), calcium decreased (30%), ALT increased (26%), urate increased (25%), LDH increased (24%), potassium increased (22%), AST increased (22%), ALP increased (20%), glucose decreased (20%), creatinine increased (19%), and sodium increased (15%). Grade 4 laboratory abnormalities in >15% of patients treated with AV include absolute neutrophil count decreased (15%). Serious adverse reactions occurred in 25% of patients receiving AV. The most common serious adverse reactions (=2%) were COVID-19 including COVID-19 pneumonia (9%), second primary malignancies (2.7%), and neutropenia (2.1%). Fatal adverse events occurred in 3.4% of patients. The most common fatal adverse events included COVID-19 and COVID-19 pneumonia. Treatment discontinuation of CALQUENCE due to adverse reactions occurred in 8% of patients receiving AV.