Autologous and Allogeneic Donor Transplantation for Mantle Cell Lymphoma in Rituximab Era: Impact of Pre-Transplant Burden On Survival.
Authors: Magnusson Erik A , Cao Qing , Linden Michael A. , Burns Linda J , Weisdorf Daniel J. , Bachanova Veronika 
Published: October 2019

Abstract
Abstract 3092
The survival for patients with mantle cell lymphoma (MCL) can be prolonged by the use of rituximab-containing intensive chemotherapies and hematopoietic cell transplantation (HCT). However, the optimal application of autologous and allogeneic HCT in the rituximab era remains uncertain.
We report 66 patients with MCL who underwent HCT (38 autologous and 28 allogeneic) at the University of Minnesota between 1999–2010. Eighty eight percent received a Rituximab-containing induction chemotherapy. Autologous HCT patients were older (66% were ≥60 years of age), 70% were in CR1 and all except 1 were chemosensitive. Two patients had minimal residual disease in the marrow (MRD) and two-thirds were PET negative at the time of transplant. Allogeneic HCT patients were younger (85% were <60 years old), 19% were in CR1 and 21% had chemo-resistant disease. At the time of transplant, 80% of allogeneic patients were PET positive and 18% of patients had detectable marrow MCL. Allogeneic recipients had a significantly longer time from diagnosis to transplant (allo 17.7 months vs auto 7.6 months; p≤0.01).
At a median follow-up of 3.5 years (range 1.1–9.2 years), the 5-year disease free survival (DFS) and overall survival (OS) of the autologous cohort were 59% and 62%, respectively (Table). In univariate analyses for DFS, younger age, absence of splenic and extranodal disease at diagnosis and shorter time to transplant were significantly associated with better survival (age <60 vs. ≥60 yrs 92% [95 CI 57–99%] vs. 43%[95 CI 18–66%]; p=0.04; extra nodal disease positive 25% [95 CI 2–63%] vs negative 77% [95 CI 48–91%]); p=.02; diagnosis to HCT time <8 months vs. ≥8 months 79% [95 CI 51–92%] vs 32% [95 CI 7–62%]; p=0.03). Patients with residual disease pre auto HCT (PET scan + and/or MRD) had significantly worse DFS (residual disease positive: 46% (95 CI 14–73%) vs negative 68% (95 CI 33–87%); p=0.04). The type of induction chemotherapy, disease status (CR1 vs other), blastoid variant or comorbidity index did not impact DFS or OS. The cumulative incidence of relapse and treatment related mortality (TRM) are shown. Notably, none of the patients with negative pre auto- transplant PET scan and lack of MRD relapsed at 2 years (p=<.01). In multivariate analysis, residual lymphoma (by PET or MRD pos) was the single significant factor associated with 5-fold lower rate of DFS compared to no residual disease (HR: 5.26 (96% CI 1.17–23.55); p=0.03).
Twenty-eight patients received allogeneic transplants (17 sibling donor, 10 umbilical cord blood, 1 unrelated donor). Half were transplanted using a reduced intensity conditioning (RIC) regimen and five patients failed a prior autograft. At a median follow-up of 6.7 years (range 1–10.3 years), the 5-year DFS and OS were 34% and 52%, respectively (Table). In univariate analysis the 5 year DFS was not significantly affected by chemosensitivity, disease status, PET positivity or MRD prior to transplant (Chemo sensitive: 41% (95 CI 20–61%) vs. resistant 17% (95 CI 1–52%) p=.38; CR1/PR1 40% (95 CI 5–75%), resistant 17% (95 CI 1–52%%), relapse 42% (95 CI 18–65) p=.66; PET pos 33% (95 CI 10–59%) vs PET neg 67% (95 CI 5–95%) p=.63). DFS following myeloablative (MA) conditioning was similar to that of RIC (43% [95 CI 16–68%] vs. 27% [95 CI 8–50%]; p=.57); MRD not shown). OS was not significantly affected by PET or marrow status prior to HCT. The cumulative incidence of 2 year relapse and 1 year TRM are shown. No relapses occurred in the MA cohort compared to a 29% relapse rate (95 CI 6–53%) after RIC HCT (p=.08). Conversely, 2 year TRM for allograft recipients was 2 times higher with MA conditioning (33% (95 CI 7–59%) compared to RIC (15% (95 CI 0–32%); p=.29).
Survival of MCL patients post autologous and allogeneic HCT has improved in the last decade. Long-term disease control is observed following autologous HCT in CR1 or for relapsed MCL, particularly if a PET negative state can be attained pre-transplant. Patients with more advanced disease and higher MCL burden prior to HCT can benefit from allogeneic transplantation. Novel therapies designed to better control MCL pre-transplant and to reduce post-transplant relapse after RIC HCT may further improve survival.
Transplant Type 5 yr DFS (95% CI) 5yr OS (95% CI) 2 yr Relapse (95% CI) 1 yr TRM (95% CI) Autologous 59% (37-76%) 62% (39-79%) 14% (3-24%) 5% (0-12%) Allogeneic 34% (17-51%) 52% (32-69%) 25% (8-43%) 19% (4-34%)

Disclosures:
No relevant conflicts of interest to declare.