On November 5, 2020, a marketing authorization valid through the European Union (EU) was issued for
acalabrutinib monotherapy or
acalabrutinib in combination with
obinutuzumab (AcalaObi) in adult patients with treatment-naïve (TN)
chronic lymphocytic leukemia (CLL) and also for
acalabrutinib monotherapy in adult patients with relapsed or refractory (RR) CLL.
Acalabrutinib inhibits the
Bruton tyrosine kinase, which plays a significant role in the proliferation and survival of the disease.
Acalabrutinib was evaluated in two phase III multicenter randomized trials. The first trial (ACE-CL-007) randomly allocated
acalabrutinib versus AcalaObi versus
chlorambucil plus
obinutuzumab (ChlObi) to elderly/unfit patients with TN CLL. The progression-free survival (PFS), as assessed by an independent review committee, was superior for both the AcalaObi (hazard ratio [HR], 0.1; 95% confidence interval [CI], 0.06-0.17) and
acalabrutinib (HR, 0.2; 95% CI, 0.13-0.3) arms compared with the ChlObi arm. The second trial (ACE-CL-309) randomly allocated
acalabrutinib versus
rituximab plus
idelalisib or
bendamustine to adult patients with RR CLL. Also in this trial, the PFS was significantly longer in the
acalabrutinib arm (HR, 0.31; 95% CI, 0.20-0.49). Adverse events for patients receiving
acalabrutinib varied across trials, but the most frequent were generally
headache,
diarrhea,
neutropenia,
nausea, and
infections. The scientific review concluded that the benefit-risk ratio of
acalabrutinib was positive for both indications. This article summarizes the scientific review of the application leading to regulatory approval in the EU. IMPLICATIONS FOR PRACTICE:
Acalabrutinib was approved in the European Union for the treatment of adult patients with
chronic lymphocytic leukemia who have not received treatment before and for those who have received
therapy but whose disease did not respond or relapsed afterward.
Acalabrutinib resulted in a clinically meaningful and significant lengthening of the time from treatment initiation to further disease relapse or patient's death compared with standard
therapy. The overall safety profile was considered acceptable, and the benefit-risk ratio was determined to be positive.