Dr Khan on the Role of Acalabrutinib in the Current CLL Treatment Paradigm

"We have data [with this agent] both in the frontline and relapsed/refractory setting, provided patients haven’t progressed on a BTK inhibitor in the frontline [setting]. [Therefore, in clinical practice,] there’s flexibility [to choose] whether [acalabrutinib is used as a] single agent or in addition to obinutuzumab. We have seen deeper responses [with the addition of obinutuzumab], and perhaps adding obinutuzumab can speed up remission."

Cyrus M. Khan, MD, an assistant professor of medicine at the Drexel University School of Medicine and the assistant director of the Stem Cell Transplant Program at the Allegheny Health Network Cancer Institute, discussed the evolving role of acalabrutinib (Calquence) in the management of chronic lymphocytic leukemia (CLL).

Acalabrutinib is a second-generation BTK inhibitor, Khan began. It received FDA approval for the treatment of both patients with treatment-naive and relapsed/refractory CLL and small lymphocytic lymphoma (SLL) in November 2019. This regulatory decision based on findings from the phase 3 ELEVATE-TN (NCT02475681) and ASCEND (NCT02970318) trials.

In the frontline setting, acalabrutinib demonstrated efficacy as monotherapy and in combination with the anti-CD20 antibody obinutuzumab (Gazyva), Khan detailed. The combination arm of ELEVATE-TN showed deeper responses compared with acalabrutinib alone, offering potential clinical benefit for patients presenting with autoimmune complications associated with CLL, Khan reported. This flexibility is one of the differentiating factors between acalabrutinib and other BTK inhibitors, and allows clinicians to tailor therapy based on disease characteristics and patient comorbidities, he explained.

In the relapsed/refractory setting, the ASCEND trial compared acalabrutinib with ibrutinib (Imbruvica), Khan continued. Although progression-free survival outcomes were comparable, acalabrutinib was associated with a lower incidence of adverse effects, particularly atrial fibrillation, atrial flutter, and bleeding, he noted. These safety data support the use of acalabrutinib in patients with cardiovascular risk factors or those who are intolerant to first-generation BTK inhibitors, Khan concluded.