Post-Transplant Bortezomib Maintenance Yields No Positive Effect in MCL

Findings from a phase 2 clinical trial demonstrated no positive effect from bortezomib maintenance therapy after transplantation in young patients with mantle cell lymphoma (MCL) but did confirm the importance of cytarabine therapy for induction (Br J Haematol. 2020 Mar 9. Epub ahead of print).

“Rituximab-containing induction followed by autologous stem cell transplantation (ASCT) is the standard first-line treatment for young mantle cell lymphoma patients. However, most patients relapse after ASCT,” explained Jeanette K. Doorduijn, MD, PhD, Haematology, Erasmus MC Cancer Centre, Rotterdam, Netherlands, et al.

Using a cohort of 140 patients (median age, 57 years) with MCL, Dr Doorduijn and co-investigators evaluated the use of a chemo-immuno regimen and ASCT with or without maintenance therapy with bortezomib in this setting.

All patients received induction comprising 3 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), 2 cycles of high-dose cytarabine, BEAM (carmustine, etoposide, cytarabine, melphalan), and ASCT. Those with a response to induction were then randomized to receive bortezomib 1.3 mg/m² every 2 weeks as maintenance therapy for 2 years or observation.

Ultimately, 135 patients were deemed eligible, including 115 (85%) who proceeded to ASCT, and 60 (44%) who were randomized. After a median follow-up time frame of 77.5 months, the 5-year event-free survival (EFS) and overall survival (OS) were 51% (95% CI, 42%-59%) and 73% (95% CI, 65%-80%), respectively.

According to the investigators, the median follow-up of randomized patients still alive was 71.5 months, and patients given bortezomib maintenance therapy had a 5-year EFS and OS of 63% (95% CI, 44%-78%) and 90% (95% CI, 72%-97%), respectively. Those who were randomized to undergo observation had 5-year PFS and OS of 60% (95% CI, 40%-75%) and 90% (95% CI, 72%-97%), respectively.

“In conclusion, although the outcome of young patients with MCL is still improving, the absence of a plateau in the EFS after induction therapy, including ASCT, demands both improvements in the induction therapy and interventions thereafter,” Dr Doorduijn and colleagues said.

“Our study confirmed the important role of ARA‐C [cytarabine] in the induction of young MCL patients. There was no indication that bortezomib maintenance after ASCT may improve outcome of MCL patients after ASCT. Other options, especially BTK inhibitors such as ibrutinib, may be explored to reduce relapse after ASCT,” they added.—Hina Porcelli