The optimal time and clinical implications of measurable residual disease detection in mantle cell lymphoma

Recent advances in measurable residual disease (MRD) technology have significantly enhanced predictive accuracy for outcomes in various hematologic malignancies, serving as a crucial surrogate endpoint. However, in mantle cell lymphoma (MCL), identifying the optimal timing for MRD assessment and understanding the prognostic implications of MRD dynamics remain challenging, primarily due to limited extensive MRD data. Our study encompassed 102 patients with MCL, all presenting with clonal B-cell involvement in bone marrow as determined by multiparametric flow cytometry (MFC). MRD evaluations were conducted every two cycles. 75.5% (77/102) achieved MRD negativity during induction therapy. We found the MRD status at the end of four cycles treatment had the best predictive ability for survival (HR = 3.2, C-index = 0.664). 32 of 77 patients (41.6%) had a rapid tumor burden reduction and achieved MRD negativity within two cycles treatment. Notably, this swift shift to MRD negativity was observed more frequently in patients classified as MIPI high-risk. However, this rapid clearance of MRD did not confer any prognostic benefit to these patients. Subgroup analyses revealed that MRD negativity held prognostic value in almost all categories, except for those with blastoid/pleomorphic morphology. MRD assessment serves as a valuable complement to the traditional response evaluation, particularly benefiting for patients attaining partial remission. These findings highlighted the importance of MRD detection during response evaluation of MCL therapy and determined that after four treatment cycles is the best MRD detection timepoint.