Long-term acalabrutinib monotherapy was shown to be safe and efficacious in patients with previously untreated chronic lymphocytic leukemia (CLL), according to the results of a phase 1/2 study published in Blood.

The multicenter US study (ClinicalTrials.gov Identifier: NCT02029443) sought to determine the recommended dose, safety, efficacy, pharmacokinetics, and pharmacodynamics of acalabrutinib in patients with symptomatic untreated CLL. A total of 99 patients were enrolled from August 15, 2014 to December 10, 2015.

The median age of the cohort was 64 years (range, 33-85 years), 67% were men and 47% had baseline Rai stage III to IV. Participants received at least 1 dose of acalabrutinib for a median of 52 months (range, 0.2-60 months), administered orally 200 mg once daily or 100 mg twice daily until progression or intolerance.

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After a median of 53 months on treatment, 85 patients (86%) remained on therapy. Among the 14 patients who discontinued therapy, adverse events (AEs) were the most frequently reported reason (n=6).

The overall response rate (ORR) in the cohort was 97%, including a complete response in 7% and partial response in 90%. The median time to first response was 3.7 months (range, 2-22 months), and the median time to complete response was 33 months (range, 22-55 months).

The ORR was 100% in patients with unmutated immunoglobulin heavy-chain variable gene, del(17p), mutated tumor protein 53, and complex karyotype. The median duration of response (DOR) was not reached, and the estimated 48-month DOR was 97% (95% CI, 90%-99%).

The most common (≥20% all grades) AEs that occurred were diarrhea (51%), headache (45%), upper respiratory tract infection (44%), contusion (42%), and arthralgia (42%). Serious AEs were reported by 38 patients (38%), of which the most frequent were pneumonia (n=4), sepsis (n=3), and (n=2) each for influenza, pancreatitis, prostate cancer, pyrexia, sinusitis, and urinary tract infection.

Infections of all grades occurred in 83 patients (84%), with 15 patients (15%) having grade 3 or 4 infection. Headache of all grades was observed in 45 patients (45%) and most were grade 1.

The investigators noted limitations in their results compared with larger phase 3 global studies that have greater variation in patient populations, regional representation, and treatment duration.

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

Disclosures: This clinical trial was supported by Acerta Pharma, a member of the AstraZeneca Group, and Acerta Pharma provided the study drug. Several of the study authors reported affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Byrd JC, Woyach JA, Furman R, et al. Acalabrutinib in treatment-naïve chronic lymphocytic leukemia. Blood. Published online March 30, 2021. doi:10.1182/blood.2020009617