In November 2019, acalabrutinib was approved by the FDA for the treatment of adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma. An updated analysis of a study of patients with relapsed/refractory CLL shows that patients continue to respond to acalabrutinib as monotherapy after 3½ years of treatment.
The extended follow-up from the phase 2 study was presented by Richard R. Furman, MD, Weill Cornell Medicine, New York City, and colleagues at the 2019 meeting of the American Society of Hematology.
At the extended follow-up, the overall response rate (ORR) was 94%, indicating that the large majority of patients continue to benefit from acalabrutinib after an extended period of treatment, said Dr. Furman. In addition, the incidence of adverse events decreased over time, suggesting that acalabrutinib’s long-term tolerability is excellent.
The study enrolled 134 patients who had relapsed or refractory CLL after at least 1 prior therapy. In the phase 2 portion, patients received oral acalabrutinib 100 mg twice daily until their side effects were intolerable or the drug no longer worked. Study end points included ORR, progression-free survival (PFS), duration of response, and safety, with a post hoc analysis for event-free survival.
At the data cutoff (January 4, 2019), patients had been treated with acalabrutinib for a median of 41 months (range, 0.2-58 months). The median age of the patients was 66 years (range, 42-85 years).
The 94% ORR included 4% of patients with a complete response and 84% with a partial response, and 6% with a partial response with lymphocytosis. The median PFS (the length of time the patient was alive without disease progressing), duration of response, and event-free survival (the length of time after treatment that the cancer did not recur or progress) were not yet reached. Response rates were similar in high-risk subgroups, such as those with unmutated IGHV (95%), chromosomal deletions (del[17p], 93%; del[11q], 95%), and complex karyotype (90%).
The estimated percentage of patients who were still responding at 45 months was 63%, the estimated percentage alive at 45 months without disease progression was 62%, and the estimated percentage without recurrence or progression at 45 months was 58%.
The most common adverse events were diarrhea, which occurred in 52% of patients; headache, reported by 46%; and upper respiratory tract infection, reported by 37%. Grade ≥3 adverse events occurred in 66% of patients and included neutropenia (14%), pneumonia (11%), hypertension (7%), anemia (7%), and diarrhea (5%). Adverse events of interest included atrial fibrillation (7%, all grades; 3%, grade ≥3) and major bleeding events (5%, all grades; 3%, grade ≥3).
Most patients (56%) remained on treatment. Treatment was discontinued due to adverse events in 17 patients. The adverse events that led to treatment discontinuation in more than 1 patient included pneumonia (n = 4), anemia (n = 2), neutropenia (n = 2), and thrombocytopenia (n = 2).
