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“Collectively, these results support acalabrutinib (Calquence) use in upfront CLL,” said Dr. John C. Byrd. “This is compounded and supported by two additional phase III studies that have been completed with this agent.”
Long-term data presented at the 2020 ASCO Virtual Scientific Program demonstrated that Calquence (acalabrutinib) is safe and effective in patients with treatment-naïve chronic lymphocytic leukemia, supporting its use in the front line setting in this population.
“Targeted inhibition of Bruton's tyrosine kinase, or BTK, has improved clinical outcome in patients with relapsed and treatment-naive CLL,” Dr. John C. Byrd, co-leader of the Leukemia Research Program at The Ohio State University Comprehensive Cancer Center — Arthur G. James Cancer Hospital, said during a pre-recorded presentation. “Acalabrutinib is a selective BTK inhibitor that has demonstrated less off-target activity in vitro as compared to other BTK inhibitors, such as ibrutinib.”
The Food and Drug Administration in 2019 granted supplemental approval to Calquence to treat adults with treatment-naïve relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
Byrd and colleagues presented mature results of the first phase 2 trial to evaluate the use of Calquence in patients with previously untreated, treatment-naïve CLL.
In the expansion phase of the ACE-CLL-001 study, 99 patients (with a median age of 64 years) received Calquence 100 milligrams (mg) twice a day (62) or 200 mg (37) once a day. Patients received the study drug until their disease progressed or they reached an unacceptable toxicity.
Although patients were initially enrolled in the once daily or twice daily arm, the researchers determined that twice daily dosing was possibly better and converted all patients to receive the 100 mg dose.
Safety was the study’s primary endpoint. Additional endpoints included investigator-assessed response, time it took disease to respond to therapy, duration of response and time a patient remained free of certain complications or events after treatment ended (event-free survival).
Following a median follow up of 53 months, 86% of patients remained on study drug. The most common reasons for discontinuation included report of adverse events (6%), disease progression (3%) and withdrawal of consent (2%).
The most common side effects included diarrhea (52%), headache (45%), upper respiratory tract infection (44%), joint pain (42%), and bruising (42%). Most of the side effects associated with Calquence went away as patients remained on therapy, according to Byrd.
Serious side effects occurred in 38% of patients, with pneumonia (4) and sepsis (3) being the only two that occurred in more than two of the participants. Two patients died while receiving study drug, however neither death was considered related to treatment.
All-grade events of clinical interest included infection (84%), bleeding events (66%, and hypertension (22%). However, of note according to Byrd, no patient discontinued Calquence treatment as a result of hypertension, bleeding or atrial fibrillation.
A median duration of response, as well as an event-free survival median response was not reached. The overall response rate associated with treatment was 97%, with 7% of patients achieving a complete response. The median time to response was 3.7 months.
“To summarize, acalabrutinib monotherapy in this study produced a very high and durable response, regardless of high-risk genomic characteristics seen in previously untreated CLL. The adverse events with acalabrutinib were generally mild with only a small subset of patients discontinuing therapy due to adverse events,” Byrd said. “Collectively, these results support acalabrutinib use in upfront CLL. This is compounded and supported by two additional phase 3 studies that have been completed with this agent.”