Mantle Cell Lymphoma: Predictive Value of Measurable Residual Disease With Rituximab Maintenance

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In an analysis from the European Mantle Cell Lymphoma Elderly Trial reported in the Journal of Clinical Oncology, Hoster et al found that outcomes with rituximab maintenance were better in patients aged ≥ 60 years with mantle cell lymphoma who had measurable residual disease (MRD)-negative vs MRD-positive status after induction therapy.

In the trial, 560 previously untreated patients were randomly assigned between January 2004 and October 2010 to rituximab vs interferon-alpha maintenance after response to rituximab, fludarabine, cyclophosphamide (R-FC) vs rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

Key Findings  

The efficacy of rituximab maintenance in clinical remission was observed for MRD-negative patients at the end of induction for progression-free survival (hazard ratio [HR] = 0.38, 95% confidence interval [CI] = 0.21–0.63) and overall survival (HR = 0.37, 95% CI = 0.20–0.68). Benefit was particularly marked in patients who had received R-CHOP; hazard ratios were 0.23 (95% CI = 0.10–0.52) for progression-free survival and 0.19 (95% CI = 0.07–0.52) for overall survival.

Rituximab maintenance was less effective in MRD-positive patients, with hazard ratios for progressive-free survival of 0.51 (95% CI = 0.26–1.02) overall and 0.59 (95% CI = 0.28–1.26) after R-CHOP induction. The hazard ratio for overall survival was 0.80 (95% CI = 0.34–1.84).

R-FC was associated with more frequent and rapid MRD clearance vs R-CHOP. MRD positivity in clinical remission after induction was associated with a median time to clinical progression of approximately 1 to 1.7 years after R-CHOP, with a shorter interval observed after R-FC.

The investigators concluded, “The results confirm the strong efficacy of rituximab maintenance in patients who are MRD-negative after induction. Treatment de-escalation for MRD-negative patients is discouraged by our results. More effective consolidation strategies should be explored in MRD-positive patients to improve their long-term prognosis.”

Christiane Pott, MD, PhD, Hämatologie und Internistische Onkologie Universitätsklinikum Schleswig-Holstein, Campus Kiel, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the European Commission within the European MCL Network, Lymphoma Research Foundation, and others. For full disclosures of the study authors, visit

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