Mantle Cell International Prognostic Index (MIPI) Is a Strong Predictor of the Outcome of Mantle Cell Lymphoma (MCL) in the Rituximab (R) Era.

A new prognostic clinical index (MIPI) and a biological one with cell proliferation (Ki-67) evaluation (MIPIb), were defined specifically for MCL to give a more reliable estimation of outcome (Hoster 2008). Aim of our analysis was to test MIPI and MIPIb on a retrospective series of MCL patients treated with R-chemotherapy.

Between 1999 and 2008, 136 MCL at diagnosis consecutively treated in five institutions entered into the study. Histology was centrally reviewed. Clinical characteristics were: median age 62 (37-84) years, 78% stage IV, 73% with bone marrow involvement and 15% with blastoid variant. First-line treatments were: R-high-dose chemotherapy with Autologous Stem Cell Transplantation (R-HDC) in 48 patients, R-Fludarabine based chemotherapy in 22, R-CHOP-like in 50 and other R containing regimens in 16. Ki-67 evaluation was performed in 93 patients; 43 were not, due to inadequate pathological materials. Overall Survival (OS) and failure-free survival (FFS) curves were estimated both overall and stratified by MIPI, MIPIb and IPI score. Differences between curves were tested using the 2-tailed log-rank test. In order to quantify the predictive discrimination of MIPI, MIPIb and IPI scores, in a subgroup of 84 patients fulfilled MIPI, MIPIb and IPI scores, a Cox's model analysis and univariate logistic models (with death and failure event as binary outcomes) were fitted and the area under the receiver operating characteristic (ROC) curves (c-index) was estimated.

Prognostic index stratification was as follows: according to MIPI 45 patients (33%) were at low-risk (LR, 0-3), 36 (26%) at intermediate-risk (IR, 4-5), 43 (32%) at high-risk (HR, >5) and 12 missing; according to MIPIb 70 patients (51%) were at LR (0-5.699), 7 (5%) at IR (5.7-6.499), 16 (12%) at HR (>6.5) and 43 missing; according to IPI 38 patients (28%) were at LR, 41 (30%) at LIR, 47 (35%) at IH-HR and 10 missing. Responses were as follows: complete 74, partial 29, no response 22, not yet evaluable 11. With a median follow-up of 28 months, 2-year OS was 80% (95% CI:71%-86%) and 2-year FFS was 60% (95%CI: 51%-69%). 2-year OS and 2-year FFS rates according to MIPI, MIPIb and IPI were shown in table 1. Eighty-four patients had all the factors to accurately calculate MIPI, MIPIb and IPI; in this subgroup, an univariate logistic model and a Cox's model including the time at the event were performed. The c-index and Cox-index for death event were 73% and 77% for MIPI, 72% and 73% for MIPIb, 67% and 65% for IPI respectively; the c-index and Cox-index for failure event were 66% and 72% for MIPI, 66% and 65% for MIPIb, 67% and 64% for IPI respectively. A further analysis for death event was performed to adjust the effect of MIPI for other known risk factors (Ann-Arbor stage, Bone Marrow involvement, blastoid variant, number of extranodal sites). In a Cox model, MIPI score and number of extranodal sites were confirmed as independent predictors of death event: adjusted hazard ratio was 8.75 (95%CI: 3.14-24.4, p=<.0001) for MIPI-HR group vs MIPI-LR, and 5.97 (95%CI: 0.80-44.59, p=.082) for at least one extranodal site.

MIPI score was confirmed as a strong predictor of death event in MCL retrospective patients treated with R-chemotherapy regimens. New therapeutic strategies are warranted to improve the outcome of MCL namely in MIPI-HR group.

Ladetto:CELGENE: Honoraria; JANSSEN-CILAG: Research Funding. Vitolo:Roche:.