Acalabrutinib for Relapsed and Refractory CLL and SLL

ASCEND is a phase 2 multicenter study that was designed to evaluate the efficacy and tolerability of acalabrutinib, a Bruton tyrosine kinase inhibitor. Patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) were eligible for this study if they relapsed after, or were refractory to, 1 or more prior treatments.

Oral acalabrutinib was administered twice daily until disease progressed or until toxicity became unacceptable. Response rates were assessed using criteria of the International Workshop on Chronic Lymphocytic Leukemia 2008 with modification for lymphocytosis (increased white blood cells).

A total of 134 patients with relapsed and refractory CLL/SLL received at least 1 dose of acalabrutinib in the ASCEND trial. Their median age was 66 years, and they had received a median of 2 prior therapies. Patients stayed on acalabrutinib treatment for a median of 41 months.

Most of the side effects reported by patients taking acalabrutinib were mild to moderate. The most common side effects were diarrhea (52%), headache (51%), and upper respiratory tract infection (37%). Severe side effects occurred in 66% of patients. The most common severe side effects were low white blood-cell count (14%), pneumonia (11%), high blood pressure (7%), anemia (7%), and diarrhea (5%). Atrial fibrillation was observed in 7% of patients; 3% of these cases were severe. Major bleeding occurred in 5% of patients; 3% of these cases were severe.

Acalabrutinib was discontinued for 13% of patients in the ASCEND trial due side effects. Side effects leading to discontinuation included pneumonia, anemia, low platelet counts, and low white blood-cell counts.

The response rate for acalabrutinib, including partial responses with elevated white blood cells, was 94%. Four percent of patients had a complete response, 84% had a partial response, and 6% had a partial response with elevated white blood cells. Median duration of response, median progression-free survival, and median event-free survival have not yet been reached.

At 45 months, most (62%) patients receiving acalabrutinib were progression-free, and 58% of these patients were event-free. Responses were seen regardless of genomic features, including unmutated IGHV, chromosomal deletions, and complex karyotype.

Researchers concluded that these updated study results validate earlier reports of acalabrutinib’s efficacy for the treatment of relapsed and refractory CLL/SLL. This study provides new data related to duration of response and shows that acalabrutinib is a tolerable drug with a low rate of major bleeding events.

Abstract 3039. ASH 2019.