The targeted regimen combines Calquence (acalabrutinib) tablets with Venclexta (venetoclax) for adults with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
CLL and SLL are slow-growing cancers of B lymphocytes, a type of white blood cell.
CLL and SLL are essentially the same disease and are caused by the same underlying cause —overproduction of abnormal B cells that have impaired immunological functions. But their names and clinical features depend on the location of these tumor cells. In CLL, the cancer cells are present mainly in the blood, whereas in SLL, they are found mainly in the lymph nodes. During the course of the illness, these cancer cells build up in the blood, bone marrow, lymph nodes, and spleen. As these abnormal B cells crowd the bone marrow, the production of normal white blood cells, red blood cells, and platelets decreases, leading to infections, anemia, and bleeding.
Why Was It Approved?
The FDA’s decision was based on data from a clinical trial that showed that Calquence combined with Venclexta is safe, effective, and well tolerated and that compared with standard chemoimmunotherapy, it helps patients with previously untreated CLL or SLL live longer without their disease getting worse. The study included adults with previously untreated CLL who did not have certain high-risk gene changes (del[17p] or TP53 mutation). Patients were randomly assigned to receive either the Calquence plus Venclexta (AV) combination therapy with or without obinutuzumab or standard chemoimmunotherapy chosen by the health care professional (fludarabine plus cyclophosphamide plus rituximab or bendamustine plus rituximab). The AV combination therapy (with or without obinutuzumab) was given for a fixed duration of 14 cycles of 28 days each, and chemoimmunotherapy was given for six cycles, according to their specific regimens. The main goal was to see how long patients lived without their cancer getting worse, known as progression-free survival (PFS). After a median follow-up duration of 42.6 months, the median PFS for the AV group was not reached because many patients were still doing well, while it was 47.6 months for the standard chemoimmunotherapy group. Additionally, the risk for disease progression or death was 35% lower with the AV combination therapy than with standard chemoimmunotherapy. Over a median follow-up duration of 41 months, fewer patients in the AV group than in the chemoimmunotherapy group (6% vs. 14%) died, indicating a significant survival benefit with the combination therapy. Common side effects reported with the Calquence plus Venclexta regimen included headaches, diarrhea, muscle or bone pain, tiredness, bruising, and rash. Blood tests showed low hemoglobin, blood glucose, and calcium levels; decreased platelet and lymphocyte counts; elevated sodium, potassium, creatinine, and urate levels; and changes in certain liver enzyme levels. In some patients, grade 4 lab abnormalities such as low neutrophil count (neutropenia) were reported. Serious adverse reactions occurred in 25% of patients receiving AV combination therapy, and serious infections or those of grade 3 or higher were seen in 14% of patients.
What Do I Need to Know?
Calquence is taken by mouth about every 12 hours, starting in cycle 1 and continuing for up to 14 cycles. Venclexta is added in cycle 3 starting at 20 milligrams once daily, and the dose is slowly increased weekly over five weeks up to the full daily dose and is continued for a total of 12 cycles. The tablets have to be swallowed whole with water — do not chew, crush, dissolve, or cut them. If you miss a dose of Calquence, take it within three hours of your usual time; if more than three hours have passed, skip the missed dose and take the next one as scheduled. Similarly, take the missed dose of Venclexta within eight hours; if more than eight hours have passed, skip the missed dose and take the next dose at your usual time. Do not take extra doses of either medicine to make up for the missed one. Before starting your treatment, tell your health care provider about all your medical conditions, including recent or planned surgery, or dental procedure, bleeding problems, heart rhythm issues, infections, or liver problems (including hepatitis B), kidney problems, any issues with electrolyte levels in your body, and about any history of high blood uric acid levels or gout. Because Venclexta causes neutropenia, your health care provider will also check your blood counts during the treatment.
