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  • Etoposide br Conclusions br Author contributions br Financia


    Author contributions
    Financial disclosures
    Formatting of funding sources
    Conflict of interest
    Introduction Mantle cell lymphoma (MCL) is a rare and aggressive subtype of B-cell non-Hodgkin lymphoma (NHL) associated with a poor prognosis. MCL was established as a distinct type of lymphoma in 1992 [1], and it Etoposide affects about 4% to 6% of all NHL patients [2]. The incidence of MCL substantially increased from 1992 to 2013 in the United States, with the largest increases observed among male, white, and elderly populations [[3], [4], [5]]. Over the past 2 decades, MCL treatment has changed dramatically. Before 1999, chemotherapy using cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) was the standard induction protocol for MCL. After 1999, a series of new regimens and novel agents to treat MCL were approved by the Food and Drug Administration (FDA). The regimens and agents approved between 1999 and 2013 included rituximab + CHOP (R-CHOP); hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD); bortezomib; the Nordic regimen (dose-intensified induction immunochemotherapy with R-CHOP [maxi-CHOP]); bendamustine; and temsirolimus [[6], [7], [8], [9], [10], [11], [12], [13], [14]]. Since 2013, lenalidomide, ibrutinib, and acalabrutinib have also been approved to treat MCL patients [[15], [16], [17]]. Most data on the effect of these newly developed regimens on MCL patients’ survival come from a limited number of randomized controlled trials (RCTs) [8,13,[18], [19], [20], [21]]. However, because of the stringent eligibility criteria for clinical trials, patients enrolled in trials tend to be healthier and younger than patients in the community, limiting the generalizability of RCTs’ conclusions. Hence, community-based studies involving large numbers of patients outside RCTs are needed. A recent population-based cohort study by Chandran et al. [22] showed that survival improved significantly over the period from 1992 to 2007, both in the overall population of MCL patients and in patients with advanced-stage tumors, suggesting that the development of novel agents and aggressive treatment regimens may have a significant impact on the survival of MCL patients.
    Discussion The findings of our study further confirmed the impact of novel agents on improved survival over time that was shown in other studies. A previous study by Chandran et al. [22] examined the survival trends in MCL in the U.S. from 1992 to 2007 using SEER database, and found no change in OS, but after adjusting for age, gender, and stage of disease, there was significant improvement in survival in both the entire group of patients and in patients with advanced tumor stage. Our study updated the data to more recent time period and the findings suggested that in both SEER and TCR, the introduction of novel agents over time had a significant impact on the survival of MCL patients. In the Nordic Lymphoma Group observational study conducted by Abrahamsson et al., the patients treated with rituximab had significantly improved OS compared to those who did not receive rituximab [29]. In another study conducted by Smith et al., the median survival for MCL patients increased by 1.5 years from 2004 to 2011 to 2012–2015 [30]. The findings from our subgroup analyses by tumor stage were consistent with those of previous studies in that significant improvement in survival was observed in MCL patients with advanced stage tumor [22,31]. Hermman et al. [31] studied the OS in MCL patients with advanced stage tumor by comparing the survival outcome of the German Low Grade Lymphoma Study Group (GLSG; 1996 TO 2004) and the Kiel Lymphoma Study Group (KLSG; 1975 TO 1986), and found that the median OS of advanced stage MCL almost doubled during the past 30 years. Chandran et al. [22] also found that patients with advanced stage tumor had an improved survival from 1992 to 2007.