Acalabrutinib Seems Safe and Efficacious in Patients With Treatment-Naïve Chronic Lymphocytic Leukemia

According to the results of a phase 1/2 study, the Bruton tyrosine kinase (BTK) inhibitor acalabrutinib was safe and efficacious, with durable remissions, in patients with previously untreated chronic lymphocytic leukemia (CLL). The findings were reported in Blood.

The single-arm study, ACE-CL-001 ( Identifier: NCT02029443), evaluated efficacy and safety of acalabrutinib monotherapy in a cohort of adult patients with treatment-naive CLL who declined or were in ineligible for chemotherapy. A total of 99 patients were enrolled and 85 were assessed in the study. The treatment was administered orally once (200 mg; n = 35) or twice (100 mg; n = 52) daily until disease progression or intolerance.

Of the 99 participants (median age, 64 years; range, 33-85), 67% were male; 47% had Rai stage III/IV disease; 62% had unmutated immunoglobulin heavy-chain variable gene; and 18% had TP53 aberrations.

The data cutoff date was August 1, 2019. The overall response rate was 97%, including 90% partial responses and 7% complete responses. Responses were consistent across all prognostic subgroups. Pharmacodynamic studies demonstrated that twice-daily dosing had significantly better median BTK occupancy than once-daily dosing; therefore, all patients were transitioned to 100 mg twice daily. The median duration of response (DOR) had not been reached at data cutoff; however, the 48-month DOR rate was 97% (95% CI, 90-99).

At a median follow-up of 53 months, 85 patients remained on treatment, and 14 patients discontinued treatment due to adverse events (AEs; n = 6; 4 second primary cancers and 2 infections), disease progression (n = 3), withdrawal of consent (n = 2), pregnancy (n = 1), and start of other anticancer therapy (n = 1).

Within the first year, the most common AEs (all grades) were headache (44%), diarrhea (33%), contusion (23%), arthralgia (22%), nausea (22%), and upper respiratory tract infection (UTRI; 20%). These AEs occurred less frequently in subsequent years, with the exception of UTRI. Serious AEs were reported in 38 patients (38%). Grade ≥3 AEs of clinical interest were infection (15%), hypertension (11%), bleeding events (3%), and atrial fibrillation (2%). There were 2 patients (2%) who died on study (1 multiple organ dysfunction during pneumonia and 1 cardiac failure during lung infection and atrial fibrillation).

“The long durability of remission seen in this trial, along with most patients remaining on therapy, suggests that acalabrutinib represents an acceptable treatment option for patients with treatment-naïve CLL and should be further evaluated in head-to-head trials with other standard-of-care therapies in this population,” the authors concluded.

Disclosure: This research was supported by Acerta Pharma. Please see the original reference for a full list of authors’ disclosures.


Byrd JC, Woyach JA, Furman RR, et al. Acalabrutinib in treatment-naive chronic lymphocytic leukemia. Blood. 2021;137(24):3327-3338. doi:10.1182/blood.2020009617