Impact of Pre-Transplant Induction Therapy on Outcomes of Patients Who Undergo Autologous Stem Cell Transplantation for Mantle Cell Lymphoma in First Complete Remission

Introduction: Mantle cell lymphoma (MCL) is a rare subtype of Non-Hodgkin lymphoma (NHL) accounting for approximately 6% of all NHL. Currently, there is no standard first line induction therapy and initial therapy is based on patient age, performance status and physician preference. Limited information is available comparing outcomes of patients who achieve first complete remission (CR1) with low intensity regimens versus high intensity regimens followed by autologous stem cell transplant (ASCT).

Methods: We conducted a retrospective chart review of adult MCL patients who underwent ASCT in CR1. Patients were divided into 2 groups based on the induction regimens: low intensity regimens ((R-CHOP, BR) versus high intensity regimens (Hyper-CVAD, Nordic Regimen, R-CHOP alternating with R-DHAP, R-DHAP). The primary objective was to compare relapse-free survival (RFS), overall survival (OS) and NRM (non-relapse mortality) between both groups.

Results: Between January 2005 and December 2016, 66 patients with CR1 received R-BEAM conditioning regimen followed by ASCT. Twenty-five patients (38%) received low intensity regimens: R-CHOP (n=21, 84%) and BR (n=4; 16%). Forty one patients (62%) received high intensity regimens: Hyper-CVAD (n=28, 68%), Nordic regimen (n=9, 22%), R-CHOP alternating with R-DHAP (n=1, 2%) and Hyper-CVAD that was changed due to intolerability (1 changed to R-CHOP and 1 to BR, n=2, 4%). Patient characteristics are summarized in the table below. Twenty-three patients (92%) in the low intensity group and 39 patients (95%) in the high intensity group had stage 4 at diagnosis. Twenty-one patients (84%) in the low intensity group and 37 patients (90%) in the high intensity group had bone marrow involvement. Three patients (12%) in the low intensity group required G-CSF plus plerixafor versus 13 patients (32%) in high intensity gr group for stem cell mobilization (p=0.1). Median day for neutrophil engraftment was 11 days in both groups, and median day for platelet engraftment was 12 days and 18 days in low intensity and high intensity regimen groups, respectively (P=0.001). Median follow-up of surviving patients was 4.18 and 4.93 years for low intensity and high intensity regimen, respectively. For low intensity regimen and high intensity regimen groups, 1-year OS was 95.7% and 97.4%, respectively (P=0.59); 1-year RFS was 92% and 89.6%, respectively (P=0.88); 1-year relapse rate was 4% and 10.4%, respectively (P=0.25); and 1-year NRM was 4% and 0%, respectively (P=0.15). Multivariable analysis identified that older age was associated with worse OS (HR 1.12, 95% CI 1.04-1.21, P=0.004), KPS < 80% was associated with higher NRM (HR 25.1, 95% CI 8.51-74.16, P<0.001) and longer days from diagnosis to transplant was associated with worse RFS (HR 1.005, 95% CI 1.001-1.008, P=0.015).

Conclusion: Our data showed no significant difference in transplant outcomes for patients who achieve CR1 with low intensity regimens when compared to high intensity regimens. Patients who received high intensity induction regimen required plerixafor more frequently for stem cell mobilization, but no difference in neutrophil or platelet engraftment was noted in the two groups.