Letter to the Editor | Published:

Rituximab maintenance therapy after autologous stem cell transplantation prolongs progression-free survival in patients with mantle cell lymphoma

Leukemia volume 28, pages 708709 (2014) | Download Citation

Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma, which is characterized by early dissemination and an unfavorable clinical course.1, 2 A common treatment for elderly MCL patients consists of chemotherapy (for example, CHOP or Bendamustin) in combination with the anti-CD20 monoclonal antibody Rituximab.3, 4 Only few patients achieve complete remission after chemo-immunotherapy, and relapse or progression occurs early within 1–3 years.1, 5 A recent report by the European MCL-Network suggests that this poor prognosis could be significantly improved by the rituximab maintenance treatment.6 In contrast, the standard treatment in younger patients (60 years) with MCL is high-dose therapy and autologous stem cell transplantation (autoSCT) after a rituximab and high-dose cytarabine (HD-ARA-C) induction regimen.4, 7, 8 However, it is not clear if rituximab maintenance treatment can further improve the prognosis in this patient population. To address this question, we compared patients with MCL who have received rituximab maintenance treatment after autoSCT with those who were followed after autoSCT without any further treatment until progression in a single-centre retrospective study.

Eligible for this analysis were all patients who underwent autoSCT for MCL at our institution between 2000 and 2012. Patients with MCL who received rituximab maintenance therapy after autoSCT within a prospective phase II trail on the value of rituximab maintenance in B-cell lymphoma (every 3 months for 2 years, NCT number 01933711) were compared with patients who were transplanted during the same time period within or outside the aforementioned trial, but did not receive rituximab maintenance therapy. End points were progression-free survival (PFS) and overall survival (OS), measured from the time of transplantation. The impact of maintenance therapy on these end points was analyzed by multivariate cox regression analysis correcting for known confounders. Rituximab maintenance was considered as a time-dependent event in order to avoid that early progression before start of rituximab maintenance therapy may compromise results. For illustration purposes Kaplan–Meier landmark plots are provided.

A total of 72 patients met the inclusion criteria. Median age was 60 years (30–74). Prior to autoSCT all patients had been exposed to rituximab-based induction and/or salvage therapy, and 45 patients had been treated with high-dose cytarabine (HD-ARA-C). AutoSCT was performed after first-line treatment in 51 patients. A complete response (CR) before autoSCT was achieved by 27 patients. Twenty-two patients from the phase-2 trial were randomized to receive post-transplant rituximab maintenance for 2 years, whereas the 50 remaining patients were followed with observation only. Patients with and without rituximab maintenance therapy did not significantly differ with regard to age, upfront autoSCT, remission status and HD-ARA-C exposure prior to autoSCT. However, there was a trend that patients who received rituximab maintenance therapy were transplanted more recently (control group: 2000–2012, rituximab maintenance group: 2002–2012, P=0.06).

Median observation time after autoSCT was 56 months. Two-year PFS and OS from autoSCT of the control group were 65% and 84%, respectively, as compared with 90% and 90%, respectively, of the rituximab maintenance group. By univariate landmark analysis, rituximab maintenance therapy was associated with significantly better PFS (hazard ratio (HR) 0.21, P=0.014; Figure 1a) but so far not OS (Figure 1b). Multivariate adjustment for age, year of transplant, achievement of CR prior autoSCT, upfront autoSCT and high-dose ARA-C treatment confirmed the beneficial impact of rituximab maintenance therapy (P=0.02, HR 0.23; Table 1). Our observation that rituximab maintenance therapy improves PFS in MCL patients after autoSCT extends the findings of a recent report that showed a benefit for rituximab maintenance after R-CHOP in elderly MCL patients. Similar results were recently shown for follicular lymphoma by the prospective Lym-01 study.9 Especially in MCL it is of particular interest to avoid relapse or prolong time to progression after autoSCT, because outcome after autoSCT failure is very poor with a median survival of approximately 17 months with a large proportion of chemo-refractory patients.10 In conclusion, our results provide a rationale for studying maintenance approaches for eligible MCL patients after autoSCT in a comparative prospective trial.

Figure 1
Figure 1

Landmark analysis of (a) progression-free survival and (b) overall survival calculated from the 6-month landmark after autoSCT for patients with MCL who underwent autoSCT and received rituximab maintenance therapy (n=20, dotted line) or no further treatment (n=38, solid line). The time is reported in months.

Table 1: Multivariate cox regression analysis of 72 patients with MCL who have undergone autoSCT

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  1. Department of Hematology, University Hospital of Heidelberg, Heidelberg, Germany

    • S Dietrich
    • , J Weidle
    • , M Rieger
    • , J Meissner
    • , A Radujkovic
    • , A D Ho
    • , P Dreger
    •  & M Witzens-Harig

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The authors declare no conflict of interest.

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Correspondence to S Dietrich.

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https://doi.org/10.1038/leu.2013.332

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