Acalabrutinib Combination Improves PFS in Previously Untreated MCL

Acalabrutinib in combination with bendamustine and rituximab significantly improved progression-free survival (PFS) in patients with previously untreated mantle cell lymphoma (MCL) aged 65 years or older, according to a recent study.

Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, and colleagues published their findings in the Journal of Clinical Oncology.

A total of 598 patients from 26 countries were randomized to receive either placebo (n=299) or acalabrutinib (100 mg twice daily) plus six cycles of bendamustine (90 mg/m² on days 1 and 2) and rituximab (375 mg/m² on day 1), followed by 2 years of rituximab maintenance (n=299). The primary endpoint was PFS, and secondary endpoints included overall response rate (ORR) and overall survival (OS). The median follow-up was 44.9 months, and the median treatment duration was 28.6 months for acalabrutinib and 24.6 months for placebo.

Patients in the acalabrutinib arm had a higher median PFS compared with patients in the placebo arm (66.4 months vs 49.6 months, respectively; HR, 0.73; 95% confidence interval [CI], 0.57 to 0.94; P=0.016), a benefit seen across all subgroups, including patients with high-risk features.

The ORR and complete response rates were also superior in the acalabrutinib arm (91.0% and 88.0%) compared with the placebo arm (66.6% and 53.5%), but there was no significant difference in OS between the two treatment groups (HR, 0.86; 95% CI, 0.65 to 1.13; P=0.27).

The percentage of patients who reported grade 3 adverse events (AEs) was comparable between the acalabrutinib group (88.9%) and the placebo group (88.2%). The most common AEs in either group were nausea, neutropenia, diarrhea, COVID-19, and headache.

After experiencing disease progression, 51 patients in the placebo arm began taking acalabrutinib. Treatment discontinuation was reported in 202 patients (67.6%) receiving acalabrutinib and 219 patients (73.2%) receiving placebo, most commonly due to AEs and disease progression.

“This did not affect the efficacy and durability of the therapy,” Dr. Wang told Blood Cancers Today regarding the discontinuation rate of acalabrutinib. “Acalabrutinib plus bendamustine-rituximab is a new standard therapy for patients who are 65 or older with untreated mantle cell lymphoma.”