Dose-Intensive (R-HCVAD) and High Dose Therapy (ASCT) Frontline Strategies More Than Double PFS Over Standard Therapy in MCL Patients

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.

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.

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).

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.

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