Consolidation with High Dose Therapy and Autologous Stem Cell Transplant Improves Survival for Patients with Mantle Cell Lymphoma
Authors: Nastoupil Loretta , Shenoy Pareen J , Ambinder Alex , Seward Miray , Nooka Ajay K. , Waller Edmund K. , Langston Amelia , Kaufman Jonathan L. , King Nassoma , Lechowicz Mary Jo , Lonial Sagar , Sinha Rajni , Flowers Christopher R. 
Published: October 2019

Abstract
Abstract 2006

Background:
Mantle cell lymphoma (MCL) comprises 5–7% of all non-Hodgkin lymphomaand remains incurable with conventional chemotherapeutic approaches. Some clinical series and trials suggest that outcomes are improved with intensive induction containing cytarabine (Ara-C) and/or the use of high dose therapy (HDT) and autologous stem-cell transplantation (ASCT) once patients (pts) achieve remission. What is not apparent are the contributions of each and which prognostic factors influence outcomes. We examined our single center experience with initial management strategies for pts diagnosed with MCL between 1995 and 2011 and compared outcomes of CHOP±R (rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone), an intensive induction regimen HCVAD±R (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate/cytarabine) in patients who subsequently underwent observation or HDT/ASCT.

Methods:
To examine the effectiveness of CHOP±R, HCVAD±R and HDT/ASCT, and the contributions of each to overall survival (OS), we conducted an IRB-approved retrospective review of consecutive cases of MCL identified from our database. Responsesfollowing the first management strategy were retrospectively assessed using International Working Group Criteria (JCO 1999). Descriptive statistics for the baseline characteristics of pts who received CHOP±R and HCVAD±R were compared using Chi-square tests. Kaplan–Meier estimation was used to evaluate OS and the treatment regimens were compared with the log-rank test. Toevaluate prognostic factors and the effects of treatment on OS, Cox proportional hazards models were used controlling for sex, race, stage, presence of B-symptoms, MIPI score, and those who underwent consolidation with HDT/ASCT.

Results:
103 ptswere identified with a median age of 58 (range 32–79 years), 27% were ≥65 years of age, 80% were male, 77% were white, 96% had an ECOG PS ≤1, 93% were advanced stage (III/IV), and the majority had a low risk MIPI score (53%). 43% (N=44) received CHOP±R (mean # of cycles 5.3, median 6, range 1–8) and the remaining 57% received HCVAD±R (N=59, mean # of cycles 4.5, median 4, range 1–12). 65% of HCVAD pts and 27% of CHOP pts received R. No significant differenceswere observed in the baseline characteristics of the two groups: age (59 years CHOP±R vs. 57 HCVAD±R, p=0.06), presence of B symptoms (32% vs. 31%, p=0.77), stage (III/IV, 91% vs. 95%, p=0.69), or MIPI score (low 50% vs. 56%, p=0.97). Of the pts who were consolidated with a transplant (N=47), median age was 58, 85% were male, 32% had B-symptoms, all had an ECOG PS ≤1, 26% had an LDH>ULN, 51% had a low MIPI, and 81% received HCVAD±R as induction. In comparison to those observed, the only significant differences were ECOG PS (8% ≥2, p=0.05) and induction regimen (63% CHOP±R, p<0.001). There were no significant differences in 5-year OS for CHOP±R: 64% (95% CI 44–79%) and HCVAD±R:68% (52–80%). There was a significant difference in 5-year OS for patients who underwent HDT/ASCT vs. those who did not consolidate with transplant (74% vs. 59%, p=0.03). 5-year OS for those treated with HCVAD±R + HDT/ASCT was not significantly different from the rest of the pts74% vs. 61% (p=0.19). After controlling for clinical confounders including sex, race, stage, presence of B-symptoms, consolidation with HDT/ASCT was associated with superior OS (HR 0.46 95% CI 0.22–0.93) while having a high MIPI score was associated with inferior OS (HR 3.79, 95% 1.59–9.01).

Conclusions:
Our single institution experience for untreated MCL pts demonstrates favorable 5-year OS independent of induction chemotherapy. Patients who underwent consolidation with HDT/ASCT had superior OS compared to those who did not.

Disclosures:
Flowers: Genentech/Roche (unpaid): Consultancy; Millennium (unpaid): Consultancy; Celgene: Consultancy; Celgene: Research Funding; Spectrum: Research Funding; Millennium: Research Funding; Gilead: Research Funding; Janssen: Research Funding.