Dose-Intensive (R-HCVAD) and High Dose Therapy (ASCT) Frontline Strategies More Than Double PFS Over Standard Therapy in MCL Patients
Authors: Mato Anthony R , Protomastro Ewelina A , Zielonka Tania , Feldman Tatyana , Rowley Scott D , Donato Michele L , Pecora Andrew L , Bhattacharyya Pritish K. , Timberg Mary , Stives Susan , Gadaleta Gabriella , Bejot Coleen , Goy Andre 
Published: October 2019

Abstract
Abstract 3658

Background:
While current front-line treatment options for the management of MCL are still debated, a growing consensus in the lymphoma community suggest that MCL pts show superior outcomes with either consolidative ASCT or dose-intensive treatment approaches over CHOP-like regimens and that cytarabine containing regimens achieve earlier and deeper (hence more durable) responses. On the other hand, such dose-intensive strategies can be difficult to administer to the elderly (a relevant issue with a median age at diagnosis of mid 60's) or in pts with comorbidities. Few studies have looked at the comparative effectiveness of initial therapies in MCL in the community setting.

Methods:
Utilizing KM and Cox regression analyses, we performed a single-center, retrospective cohort analysis to describe the survival experience of 139 MCL pts (med follow up 50 months) treated in the front-line setting with R-CHOP (n=35), R-HCVAD (n=63) or induction-chemotherapy followed by HDT-ASCT (n=41). The primary endpoints of this retrospective cohort analysis were overall (OS) and progression free survival (PFS). The proportional hazards assumption was met for this analysis.

Results:
The JTCC MCL outcomes database contains 214 total patient entries (newly dx + relapsed MCL) from 1993–2012 of which 139 pts met inclusion/exclusion criteria with complete outcomes data available. The R-CHOP, R-HCVAD and HDT-ASCT groups were comparable in terms of known prognostic factors including age (median 60), ECOG PS (median 1), MIPI score (median score 4, 30% int risk, 29% high risk) and Ki-67 (median 30% and range 5–95%). The median PFS was superior for pts treated with either R-HCVAD (53 months) or ASCT (63 months) (p=<.001, LR test, Figure) compared to R-CHOP (24 months). No significant difference (HR 1.15, p=.7, 95%CI .5–2.5) in PFS could be detected between pts age < 65 vs. those age >= 65 (n=25) treated with either R-HCVAD (med PFS 46 months) or HDT-ASCT (med PFS 54 months). Median OS favored pts treated with R-HCVAD or HDT-ASCT (103 months and 108 months respectively) over R-CHOP (67 months) but did not meet statistical significance (p=.16, LR test).

Conclusions:
These data represent the largest published single center experience of MCL patients treated in the front-line setting. Our results confirm a recent NCCN report showing benefit of dose-intensive/high dose strategies in MCL over conventional therapy with more than doubling median PFS over R-CHOP. Of notice when compared to recently updated STiL trial (Rummel ASCO 2012, abst #3) our results are c/w with a median PFS of 22 months after R-CHOP but appear superior to med PFS (35 months) seen with bendamustine-rituximab in MCL even in a subset of elderly pts >= age 65. Our results support the use of dose-intensive strategies in a fit geriatric patient population. Finally the excellent PFS seen in that setting represents a promising platform for integrating novel agents in combination and/or maintenance in future strategies to prevent recurrence and continue to improve MLC pts outcome.

Disclosures:
Mato: Genentech: Speakers Bureau; Seattle Genetics: Speakers Bureau; Millennium: Speakers Bureau; Celgene: Speakers Bureau. Feldman:Allos: Speakers Bureau; celgene: Speakers Bureau; Seattle Genetics: Speakers Bureau; Merck: Speakers Bureau. Goy:Milennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; J & J: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees.