What is the role of up-front autologous stem cell transplantation in mantle cell lymphoma?

Up-front autologous stem cell transplantation (ASCT) is the established standard of care for younger, transplant-eligible MCL patients and is associated with a prolonged progression-free survival (PFS) benefit. However, there is no randomized controlled trial data, with therapy including rituximab and cytarabine, that has established a PFS and overall survival (OS) benefit with ASCT in the modern era. Multiple retrospective studies have failed to identify an OS benefit associated with ASCT in younger MCL patients. The high-risk patient subgroup with evidence of baseline TP53 mutation has a dismal outcome with intensive chemoimmunotherapy followed by ASCT, thus up-front ASCT is not optimal for this patient subset. Ongoing randomized clinical trials will help to clarify the role of up-front ASCT in the future. For example, the ongoing European MCL Network Triangle study incorporating ibrutinib into chemoimmunotherapy induction and maintenance with and without ASCT will help define the role of ASCT in the era of novel biologically targeted agents (ClinicalTrials.gov identifier: NCT02858258). Additionally, minimal residual disease (MRD) assessment is a powerful prognostic tool in MCL, and the ongoing Eastern Cooperative Oncology Group-American College of Radiology Imaging Network E4151 study is comparing maintenance rituximab alone vs ASCT consolidation in MCL patients who achieve remission and MRD-undetectable status post induction (ClinicalTrials.gov identifier: NCT03267433). ASCT remains a highly efficacious initial therapy for younger MCL patients; however, ultimately the decision to pursue ASCT requires discussion of risks vs benefits, incorporating patient preferences and values.