Minimal residual disease (MRD) predicted relapse of mantle cell lymphoma (MCL) after treatment, with risk increasing as MRD persisted over 12 months, according to study published in Blood.

“Despite its success, many points remain to be addressed to fully establish the value of MRD detection in MCL,” the authors wrote in their report. “This is the first study investigating the role of MRD in the context of maintenance treatment in MCL.”

The open-label, phase 3 MCL0208 trial compared lenalidomide maintenance therapy or observation after autologous stem cell transplantation (ASCT) after initial treatment for 300 patients with MCL with high-dose chemoimmunotherapy. A secondary endpoint was to characterize the prognostic ability of MRD and MRD kinetics. MRD was analyzed at multiple time points during study follow-up.

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Of the 250 patients in whom an MRD marker was detectable, continued MRD positivity over time was associated with increasing risk for MCL relapse. Patients with MRD in bone marrow after chemoimmunotherapy induction and after rituximab plus high-dose cytarabine did not have an increased risk for progression. However, MRD positivity after ASCT was significantly associated with shorter TTP (hazard ratio [HR], 1.81; 95% CI, 1.02-3.20; P =.043), with risk increasing among patients with MRD at 6 months (HR, 3.82; 95% CI, 1.92-7.62; P <.001) and 12 months (HR, 5.60; 95% CI, 2.68-11.7; P <.001).

MRD positivity in bone marrow that persist for at least 1 year was significantly associated with shorter time to progression (TTP) with lenalidomide (P <.0001) or ASCT (HR, 6.93; 95% CI, 1.74-27.6; P =.006). Alternating positive and negative MRD was also associated with shorter TTP after ASCT (HR, 5.51; 95% CI, 2.02-15.0; P <.001).

MRD detection was most accurate by real-time quantitative polymerase chain reaction (RQ-PCR) compared with a simple nested PCR, as indicated by a higher risk detection for bone marrow (HR, 3.75; 95% CI, 2.37-5.93 vs HR, 2.19; 95% CI, 1.10-4.35) and peripheral blood (HR, 2.33; 95% CI, 1.46-3.70 vs HR, 1.83; 95% CI, 1.14-2.94). The use of bone marrow was prefer to peripheral blood due to a similar improvement in risk detection. The authors concluded that these data “suggest that kinetic analysis is the most effective approach to predicting outcomes in MCL patients.”

Disclosures: Some of the study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.


Ferrero S, Grimaldi D, Genuardi E, et al. Punctual and kinetic MRD analysis from the Fondazione Italiana Linfomi MCL0208 phase 3 trial in mantle cell lymphoma. Blood. 2022;140:1378-1389. doi: 10.1182/blood.2021014270