FDA Approves Acalabrutinib for CLL, SLL


Recent approval under new international Project Orbis.


The FDA has approved acalabrutinib (Calquence, AstraZeneca) for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). 

A third indication for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy is under accelerated approval and contingent upon verification and description of clinical benefit in confirmatory trials.

Acalabrutinib is a Bruton tyrosiene kinase (BTK) inhibitor that covalently bonds to BTK thereby inhibiting activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion, according to AstraZeneca’s official release.

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The approval is based upon the results of two phase 3 clinical trials, ELEVATE-TN and ASCEND. 

ELEVATE-TN included 535 patients randomly assigned into three study arms:

  • Arm 1: chlorambucil in combination with obinutuzumab

  • Arm 2: acalabrutinib (100 mg twice daily until disease progression or unacceptable toxicity) in combination with obinutuzumab

  • Arm 3: acalabrutinib monotherapy (100 mg twice daily until disease progression or unacceptable toxicity)

Overall results: 

  • Combination arm: 90% reduction of risk of disease progression or death

  • Monotherapy arm: 80% reduction in disease progression or death

  • Median time to disease progression: not yet reached (compared to 22.6 months for  chlorambucil plus obinutuzumab

ASCEND included 310 patients randomly assigned into two arms: 

  • Arm 1: calquence montherpay(100 mg twice daily until disease progression or unacceptable toxicity)

  • Arm 2: investigators choice of either rituximab plus idelalisib, or rituxiumab plus bendamustine

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“Tolerability remains an issue in the current treatment landscape of chronic lymphocytic leukemia, which may require ongoing therapy for many years,” says Jeff Sharman, MD, director of research at Willamette Valley Cancer Institute and the lead author of the ELEVATE-TN trial in a statement. “In the ELEVATE-TN and ASCEND trials comparing Calquence to commonly used treatment regimens, Calquence demonstrated a clinically meaningful improvement in progression-free survival in patients across multiple settings, while maintaining its favorable tolerability and safety profile.”

Warnings and precautions issued with the use of acalabrutinib include serious and opportunistic infections; hemorrhages; cytopenias; second primary malignancies; and atrial fibrillation and flutter.

Acalabrutinib has been known to negatively interact with CYP3A inhibitors and inducers, and gastric acid reducing agents. 

Adverse events reported with the use of acalabrutinib include anemia, neutropenia, upper respiratory tract infection, thrombocytopenia, headache, diarrhea, and musculoskeletal pain. 


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