In addition to clinical risk stratification with the Mantle Cell Lymphoma International Prognostic Index (MIPI) score, the Ki-67 proliferation score is useful for the molecular risk stratification of patients with MCL. In a 2016 study, the modified combination of the Ki-67 index and the MIPI, which incorporated a dichotomized Ki-67 proliferation index with a 30% cutoff level, differentiated survival outcomes into 4 risk groups, with 5-year overall survival ranging between 17% and 85%.

One of the newer approaches to the risk stratification of patients with MCL is the detection of alterations or deletions in the TP53 tumor suppressor gene. Alterations and deletions in TP53 have been associated with less favorable outcomes in patients with MCL, particularly those receiving chemotherapy-based treatment. In the Nordic MCL2 and MCL3 studies, mutations of TP53 (11%) and NOTCH1 (4%) and deletions of TP53 (16%) and CDKN2A (20%) were linked to unfavorable outcomes. In the randomized European MCL Younger study, simultaneous deletions of CDKN2A and TP53 were associated with dismal outcomes. An analysis of pooled data from 3 ibrutinib MCL studies found that the high-risk simplified MIPI score, bulky disease, and blastoid histology were adversely associated with overall survival and progression-free survival.

The MIPI score and TP53 frequently go hand in hand, with high-risk MIPI scores often being accompanied by TP53 mutations or deletions. The presence of simultaneous negative findings in both parameters predicts a poor prognosis.

Minimal residual disease (MRD) in MCL is another area of potential advancement. Molecular remission according to MRD status after induction treatment was highly predictive of response duration and disease progression in multiple studies of intensive treatment protocols that incorporated high-dose cytarabine and consolidative autologous stem cell transplantation, including the Nordic MCL2 and MCL3 studies and the European MCL Younger study. MRD may be one of the more robust profiling tools that will probably have more clinical use in the future.