Dr Kahl on the Outcomes of Bortezomib Plus BR in MCL

“The study showed that adding bortezomib to the bendamustine/rituximab induction did not improve the 2-year progression-free survival, [which] came in right around 75% to 80% in both arms, and [the bortezomib regimen] didn’t improve the complete remission rates either.”

Brad S. Kahl, MD, a professor in the John T. Milliken Department of Oncology in the Division of Oncology at the Washington University School of Medicine, detailed the outcomes of adding bortezomib (Velcade) to bendamustine/rituximab (Rituxan; BR) induction therapy with rituximab with or without lenalidomide (Revlimid) maintenance for the treatment of patients with mantle cell lymphoma (MCL).

An open-label, randomized, phase 2 study (NCT01415752) included 4 arms, which evaluated BR alone followed by maintenance rituximab; bortezomib plus BR and maintenance rituximab; BR followed by maintenance rituximab/lenalidomide; and bortezomib plus BR followed by maintenance rituximab/lenalidomide. The study enrolled 373 patients, of whom the median age was 67 years (range, 42-90).

Based on the 4 arms, data demonstrated that the addition of bortezomib to BR induction did not improve 2-year progression-free survival (PFS), Kahl began. At a median follow-up of 7.5 years, the median PFS was 6.4 years for patients treated with bortezomib plus BR induction vs 5.5 years for those given BR induction alone (HR, 0.90; 95% CI, 0.70-1.16). The data revealed 2-year PFS rates of approximately 75% to 80% in all arms, and complete remission rates were not improved with the addition of bortezomib, Kahl noted. Furthermore, the addition of lenalidomide as maintenance also did not improve 2-year PFS, which established that the study was not successful in identifying a superior treatment, he explained.

However, the study determined that BR induction was very effective, with a median PFS of more than 5 years, Kahl said. He emphasized that this finding was beneficial, particularly to older patients with MCL on the study. Although the study outcomes were not as investigators anticipated, he added that the induction regimen has been cemented as the backbone for building and testing other treatment strategies. Following the study, Kahl concluded that newer drugs, including the BTK inhibitors ibrutinib (Imbruvica) and acalabrutinib (Calquence), entered the treatment landscape for patients with MCL based on data from the phase 3 SHINE (NCT01776840) and ECHO (NCT02972840) trials, respectively.