From the Journals

Acalabrutinib may outperform other targeted therapies in MCL



For patients with relapsed or refractory mantle cell lymphoma (MCL), second generation Bruton’s tyrosine kinase (BTK) inhibitor acalabrutinib may offer increased response rates and better tolerability compared with other single-agent targeted therapies, based on a recent analysis.

Mantle cell lymphoma Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

Mantle cell lymphoma

Improved safety could lead to long-term benefits resulting from extended treatment duration, according to lead author Claire Telford, PhD, of AstraZeneca in Gaithersburg, Md., and colleagues. AstraZeneca manufactures acalabrutinib (Calquence).

Currently, treatment for MCL is guided by a number of clinical considerations, the investigators explained in Clinical Therapeutics.

“The type of treatment recommended for relapsed/refractory MCL depends on multiple factors, namely time to the relapse, extent of disease, previous regimens, candidacy for allogeneic stem cell transplantation, and the patient’s overall health,” they wrote.

To determine how acalabrutinib stacks up with other options, the investigators drew data from the phase 2 ACE-LY-004 trial, which tested acalabrutinib in 124 patients with relapsed or refractory MCL. After matching, the investigators compared the ACE-LY-004 outcomes from 12 other trials, in which patients received different targeted therapies.

Results pointed to higher overall response and complete response rates for acalabrutinib, compared with other single-agent targeted therapy. Specifically, acalabrutinib had a higher overall response rate, compared with ibrutinib (9.3% higher), lenalidomide (38.1% higher), temsirolimus (40.7% higher), and bortezomib (50.6% higher). For each of these, complete responses also were higher.

There was no significant difference in overall response or complete response rates between acalabrutinib and rituximab combinations – bendamustine plus rituximab, ibrutinib plus rituximab, and lenalidomide plus rituximab.

The investigators also highlighted a number of safety advantages. Compared with ibrutinib, acalabrutinib was associated with significantly fewer instances of grade 3 or 4 atrial fibrillation. Risk of grade 3 or 4 thrombocytopenia was significantly lower with acalabrutinib than with ibrutinib, bortezomib, lenalidomide, and temsirolimus.

Still, in some instances, acalabrutinib was comparatively less tolerable. It was associated with a higher risk of grade 3 or 4 infections than bendamustine plus rituximab; and anemia was more common among patients receiving acalabrutinib than among those who had lenalidomide plus rituximab or ibrutinib plus rituximab.

“This comparison of targeted therapies used in the treatment of relapsed/refractory MCL has shown that acalabrutinib has the potential to provide higher response rates, with trends for longer [progression-free survival] and [overall survival], and an improved safety profile,” the investigators wrote.

The study was funded by AstraZeneca. Dr. Telford is an employee of AstraZeneca and other authors reported financial relationships with the company.

SOURCE: Telford C et al. Clin Ther. 2019 Nov 4. doi: 10.1016/j.clinthera.2019.09.012 .

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