Five-year outcomes of the S1106 study of R-hyper-CVAD vs R-bendamustine in transplant-eligible patients with mantle cell lymphoma

Aggressive induction chemoimmunotherapy followed by high-dose chemotherapy and autologous stem cell transplant (ASCT) is a standard option for the initial management of transplant-eligible mantle cell lymphoma (MCL).1-3 However, the optimal induction regimen before ASCT is unknown. Cytarabine-based induction achieves excellent response rates and higher rates of minimal residual disease (MRD) negativity compared with anthracycline-based induction regimens.4-6 While effective, most cytarabine-based induction regimens require inpatient hospitalization and are associated with significant hematologic and nonhematologic toxicities.4-6 Rituximab-bendamustine (RB) is a less intensive, outpatient-based chemoimmunotherapy regimen with excellent long-term efficacy and good tolerability in transplant-ineligible MCL patients.7-9 However, its role as a pretransplant induction strategy has not been formerly evaluated. S1106 is a randomized phase 2 multi-institutional clinical trial comparing induction R-hyper-CVAD (rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) and methotrexate/cytarabine (RH) with RB followed by ASCT in newly diagnosed MCL patients. We previously reported that the 2-year progression-free survival (PFS) and overall survival (OS) were similar with either regimen. However, RH was more toxic than RB, had higher stem cell mobilization failure rates, and prompted protocol-specified early study closure.10 While premature closure limited the sample size, we demonstrated for the first time in a prospective setting that outpatient RB treatment can achieve excellent MRD negativity and could serve as an induction strategy worthy of further study. Given the increased survival of MCL patients,2 critical assessment of long-term efficacy and toxicity is needed. Here, we report the 5-year follow-up (FU) of the S1106 study.