Fewer patients with chronic lymphocytic leukemia (CLL) who were treated in the first line with the oral kinase inhibitor acalabrutinib alone or in combination with the monoclonal antibody obinutuzumab experienced disease progression or died compared with patients treated with obinutuzumab and chlorambucil, according to results from a new randomized phase 3 study.
In the study known as ELEVATE-TN, which was presented at the 2019 American Society of Hematology meeting in Orlando, FL, the risk for disease progression or death at a median follow-up of 28 months was reduced by 90% with the combination of acalabrutinib plus obinutuzumab compared with obinutuzumab plus chlorambucil, announced Jeff P. Sharman, MD, Director of Research at Willamette Valley Cancer Institute and Medical Director of Hematology Research for the US Oncology Network.
Acalabrutinib alone also prolonged progression-free survival compared with obinutuzumab plus chlorambucil, with an 80% reduction in the risk for progression or death.
Acalabrutinib was approved by the US Food and Drug Administration on November 21, 2019, for the treatment of CLL and small lymphocytic lymphoma. It previously demonstrated efficacy among patients with previously untreated CLL as a single agent or in combination with obinutuzumab. Acalabrutinib is a more selective tyrosine kinase inhibitor (TKI) than ibrutinib, the first TKI approved for the treatment of CLL, with less off-target kinase inhibition leading to a more favorable safety profile.
In the multicenter, open-label trial, 535 patients with previously untreated CLL were randomly assigned to either acalabrutinib alone, given twice daily; acalabrutinib in combination with intravenous obinutuzumab; or intravenous obinutuzumab in combination with chlorambucil infusions. Two-thirds of patients had high-risk CLL features.
The estimated rates of progression-free survival at 30 months were 90% with acalabrutinib plus obinutuzumab, 82% with acalabrutinib alone, and 34% with obinutuzumab plus chlorambucil.
Median overall survival (OS) was not reached in any of the groups. Acalabrutinib plus obinutuzumab reduced the risk for death by 53% compared with obinutuzumab and chlorambucil, and acalabrutinib alone reduced the risk for death by 40% versus obinutuzumab and chlorambucil. This lower risk for death in the acalabrutinib arms occurred despite an allowance for crossover with disease progression in patients who were assigned to obinutuzumab plus chlorambucil, said Dr. Sharman. Estimated OS at 30 months was 95% with acalabrutinib plus obinutuzumab, 94% with acalabrutinib alone, and 90% with obinutuzumab and chlorambucil.
Median treatment duration was 27.7 months for the acalabrutinib groups and 5.6 months for the obinutuzumab plus chlorambucil group.
Patients in the acalabrutinib groups had a lower rate of infusion-related reactions compared with the obinutuzumab-chlorambucil group (13% vs 40%). Atrial fibrillation, hypertension, and bleeding of any grade were more common in the acalabrutinib arms compared with obinutuzumab-chlorambucil. Adverse events led to treatment discontinuation by 20 patients in the acalabrutinib-obinutuzumab group, 16 in the acalabrutinib monotherapy group, and 25 in the obinutuzumab-chlorambucil group.