Intensive Treatment Strategies May Not Provide Superior Outcomes in Mantle Cell Lymphoma: Overall Survival Exceeding Seven Years in a Large Cohort of Patients Managed Primarily with Conservative Therapies.

Historically, reported outcomes in patients with mantle cell lymphoma (MCL) have been poor, with a median overall survival cited in the range of 2 to 4 years. As a consequence, recent approaches to first-line treatment have become more aggressive. Single- and oligo-center non-randomized studies with R-Hyper-CVAD and/or autologous stem cell transplant in first remission have produced 3-year overall survival >80%, prompting many to consider them as optimal standard of care. However, a substantial fraction of MCL patients are ineligible to receive these regimens due to age and comorbidities. To determine whether these interesting results might be affected by patient referral/selection biases rather than a true superiority of therapy, we evaluated outcomes from our MCL patient cohort, a group potentially shaped by similar biases but largely managed in a more conservative fashion. As progression-free survival is likely improved by aggressive treatments, our focus is on overall survival given the central importance of this endpoint.

Methods: We used pathology records to identify all patients with a diagnosis of MCL evaluated at the Weill Cornell Medical Center since 1997. Patients were considered eligible for inclusion if a date of diagnosis could be identified. In the subset where clinical records were limited, an online social security database was used to verify survival. Median overall survival was calculated according to the Kaplan-Meier method.

Results: We identified 181 patients with the diagnosis of MCL established by standard hematopathologic criteria. Forty-eight of these cases were outside consults to our pathology department without available clinical data. Of the remaining 133 patients, date of diagnosis was identified in 111 subjects. Median age at diagnosis was 64 years (range: 37–88). For the subset of patients with available prognostic information, 81% were stage IV, 75% had bone marrow involvement, 52% had an IPI of ≥3. The median overall survival (N=111) was 7.1 years (85 months with 95% C.I. 63 to 98 mo.). Three-year overall survival was 86% (95% C.I. 78% to 92%). Adequate information on therapy was available for 75 patients. Most patients were treated with CHOP-like regimens. Only 5 were treated with (R)-Hyper-CVAD or autologous stem cell transplant in first remission while an additional 4 patients received one of these regimens as subsequent therapy, Five patients survived longer than 10 years—one patient is alive at 15.4 years—despite never receiving Hyper-CVAD or autoSCT. Univariate analysis of treatment type revealed no significant effect on overall survival.

Conclusions: Our data demonstrate that single-center outcomes with conservative approaches in MCL can yield similar overall survival to that achieved with more intensive approaches at other single-centers. Therefore patient referral/selection biases may substantially account for the perceived superiority of aggressive strategies. Intensive treatment approaches for MCL should not be considered superior with respect to overall survival in the absence of long-term data from multicenter randomized trials comparing them to more conservative strategies.