Dr. Mato on Ibrutinib Versus Acalabrutinib in CLL

Anthony R. Mato, MD, MSCE, hematologic oncologist, director, CLL Program, Memorial Sloan Kettering Cancer Center, discusses differences between the use of ibrutinib (Imbruvica) and acalabrutinib (Calquence) in chronic lymphocytic leukemia (CLL).

Ibrutinib is a first-in-class BTK inhibitor that is approved in many indications, including CLL. In February 2014, the agent was approved for use in adult patients with CLL who received at least 1 prior therapy. By July 2014, the therapy received approval for adult patients with CLL and 17p deletion. By March 2016, ibrutinib received approval for use as frontline therapy. In May 2016, ibrutinib was indicated for use in combination with bendamustine and rituximab (Rituxan) for adult patients with CLL and small lymphocytic leukemia (SLL). Most recently, in January 2019, the agent was approved for use in combination with obinutuzumab (Gazyva) in previously untreated patients with CLL/SLL.

Acalabrutinib is a next-generation BTK inhibitor that is designed to be more specific to BTK with less off-target effects, says Mato. However, there are no data to definitively say that next-generation BTK inhibitors are less toxic than first-generation agents, adds Mato. On November 21, 2019, the agent was approved for the treatment of adult patients with CLL.

The 2 agents are being compared in a head-to-head trial in the relapsed/refractory setting in patients with deletion 17p or 11q. However, as no data have been reported yet, it is difficult to compare the 2 drugs. The field has longer follow-up data with ibrutinib compared with acalabrutinib, but both agents have shown significant activity, says Mato. Data from the randomized trial are expected to provide insight into the efficacy and toxicity differences among these drugs, concludes Mato.