Acalabrutinib Granted FDA Approval for Mantle Cell Lymphoma Treatment

The FDA has granted an accelerated approval to acalabrutinib (Calquence) as a treatment for adult patients with mantle cell lymphoma (MCL) following at least 1 prior therapy, based on objective response rates (ORR) in a single-arm trial.

In the 124-patient ACE-LY-004 phase II trial, the ORR was 81% with acalabrutinib, which was evenly split between complete responses (40%) and partial responses (41%). The approval for the novel BTK inhibitor arrived several months ahead of expectations under the Prescription Drug User Fee Act and followed a breakthrough therapy designation from the FDA for MCL in early August.

“Mantle cell lymphoma is a particularly aggressive cancer,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a statement. “For patients who have not responded to treatment or have relapsed, Calquence provides a new treatment option that has shown high rates of response for some patients in initial studies.”

The most common adverse events (AEs) of any grade were anemia (46%), thrombocytopenia (44%), headache (39%), neutropenia (36%), diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%), which is a known class effect for BTK inhibition. Most these bruising events were grade 1 in severity (19%). The most common grade ≥3 AEs were neutropenia (15%), thrombocytopenia (12%), anemia (10%), and diarrhea (3.2%).

The median duration of treatment with acalabrutinib was 16.6 months (range, 0.1-26.6), with 73.4% of patients receiving the medication for ≥6 months and 59.7% on treatment for ≥1 year. Overall, dose reductions due to AEs were required for 1.6% of patients and dose discontinuations were required for 6.5% of patients.

Under the accelerated approval program, full approval for acalabrutinib is contingent on findings from confirmatory trials. Currently, the phase III ACE-LY-308 clinical trial is currently evaluating acalabrutinib in combination with bendamustine and rituximab (BR) versus placebo plus BR for patients with untreated MCL.