A Powerful Predictor of Outcome in Mantle Cell Lymphoma

Status of post-treatment measurable residual disease (MRD) in peripheral blood and bone marrow correlates with clinical outcome in B-cell lymphomas. To prospectively assess the predictive value of this biomarker in mantle cell lymphoma (MCL), investigators in Italy conducted a multicenter, randomized, phase 3 trial involving 300 previously untreated MCL patients who received induction rituximab plus chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT). Patients were then randomized to maintenance lenalidomide or observation for 24 months.

Peripheral blood and bone marrow samples were obtained at multiple predetermined time points during each phase of treatment and every 6 months during and after completion of maintenance therapy. MRD analysis was performed using real-time qualitative (RQ) PCR and nested PCR for immunoglobulin loci and the CCND1 (BCL1)/IgH translocation breakpoints. The impact of MRD positivity on time to progression was determined from the time of each MRD result to disease progression or death.

Of the 300 patients, 250 (83%) had a useable MRD marker. RQ-PCR results were more predictive than nested PCR results. MRD analysis was most predictive of outcome starting 6 months after completion of ASCT. Bone marrow results were more predictive than peripheral blood results at early time points of treatment, but peripheral blood results were reliable at later time points and were recommended for long-term monitoring.