Mantle Cell Lymphoma International Prognostic Index (MIPI) was derived from a data set of 455 advanced stage MCL patients treated in series of clinical trials in Germany/Europe.
MIPI is able to classify patients into three risk groups: low risk (median survival not reached after median 32 mos follow-up and 5-year OS rate of 60%), intermediate risk (median survival 51 months) and high risk (median survival 29 months).
In addition to the 4 independent prognostic factors included in the model, the cell proliferation index (Ki-67) was also shown to have additional prognostic relevance.
When the Ki67 is available, a biologic MIPI (MIPIb) can be calculated.
According to the MIPI, patients are classified into low risk (44% of patients, median OS not reached), intermediate risk (35%, 51 months), and high risk groups (21%, 29 months), based on the 4 independent prognostic factors: age, performance status, lactate dehydrogenase (LDH), and leukocyte count.
Cell proliferation (Ki-67) was exploratively analyzed as an important biologic marker and showed strong additional prognostic relevance.
Mantle cell lymphoma (MCL) is a relatively rare lymphoma entity accounting for approximately 3% to 6% of all non-Hodgkin lymphoma (NHL) cases.
MCL has a poor prognosis with reported median overall survival (OS) of only 30 to 43 months.
Treatment results have overall been unsatisfactory.
There is a substantial variation in outcome was noted among individual cases with a small fraction of patients even achieving long lasting remissions.
The proliferation markers Ki-67 and number of mitoses, possibly the most important prognostic markers in MCL.
455 patients with advanced stage MCL entered the trials.
The median age was 60 years (34-86 years) and 76% of the patients were male.
Eighty-four percent of the patients were in Ann Arbor stage IV, 79% had bone marrow involvement.
Forty-three percent presented with B-symptoms and 9% were unable to work or bedridden.
Median age, y (range) 60 (34-86) Sex male 76%
ECOG 0, 33%
ECOG 1 58%
ECOG 2-4 9%
Stage IV, 84%
B-symptoms present 43%
Bone marrow involvement present 79% Extranodal sites more than 1, no. 32% Median no. involved nodal areas, 8
Median max. lymph node size, 4 cm Spleen involvement present, 54% 225
Median WBC count, 7.9 (1.0-764) Median lymphocyte count, 2.1 (0.35-625) Median granulocyte count, 4.2
Median monocyte count, 0.5
Median platelet count, 188
Median LDH/ULN (range) 0.86
Median hemoglobin (males),g /L, 13.3
Median hemoglobin (females),g /L, 12.4 Median albumin/ULN (range) 0.8 gm
Median β2-microglobulin/ULN 1,1
Initial cytoreductive chemotherapy comprised CHOP in 56% of the patients, 31% of the patients received R-CHOP, 11% MCP, and 2% other chemotherapy regimens.
Of the 438 patients evaluable for treatment response, 351 (80%) achieved a complete or partial remission, and 80 (18%) a complete remission.
Treatment in remission was ASCT in 80 patients, IFNα maintenance in 199 patients, and 72 patients obtained no therapy in remission.
Of the 455 patients, 159 had died and the median OS was 57 months with a median follow-up of surviving patients of 32 months.
99 patients (23%) were classified as low risk (LR), 173 patients (40%) as low intermediate risk (LIR), 119 patients (28%) as high intermediate risk (HIR), and 41 patients (9%) as high risk (HR).
The median OS was not yet reached in the LR group with a 5-year OS rate of 59%, and 61 months in the LIR group, 45 months in the HIR group and 20 months in the HR group.
LIR and HIR groups comprised together more than two-thirds of the patients and were not well separated.
ECOG performance status and LDH were prognostic for OS, whereas the number of extranodal sites was not.
Neither sex, Ann Arbor stage (III vs IV), bone marrow involvement, number of extranodal sites or number of nodal areas, nor platelet count or albumin showed prognostic relevance for OS in univariate analyses.
ECOG performance status, B-symptoms, spleen involvement, maximal lymph node size, WBC, lymphocyte, granulocyte, and monocyte counts, LDH, Hb, and β2-microglobulin had a significant impact on OS.
Mantle cell lymphoma international prognostic index (MIPI)
The median value of the prognostic score in 409 patients was 5.78.
It defines a high-risk group score ≥ 6.2).
The definition of an intermediate-risk group has the value of 5.7.
Low-risk group has a score < 5.7).
Median OS was not reached in the low risk group with a 5-year OS of 60%, and it was 51 months and 29 months in the intermediate-risk group and the high-risk group, respectively.
The MIPI prognostic score is calculated as [0.03535 × age (years)] + 0.6978 (if ECOG > 1) + [1.367 × log10(LDH/ULN)] + [0.9393 × log10(WBC count].
To make the index most practicable, weighting age, ECOG performance status, LDH, and WBC with 0 to 3 points using 3 cutpoints each and classifying patients with a total of at most 3 points as LR, patients with 4 to 5 points as IR and patients with more than 5 points as HR, yielded high concordance and good separation of OS curves.
The Mantle Cell Lymphoma International Prognostic Index (MIPI) is a clinical tool specifically developed to predict prognosis in patients with mantle cell lymphoma (MCL).
MIPI is tailored to the unique characteristics of MCL and is validated for use in both clinical trials and routine practice.
Key features of MIPI: Parameters: MIPI uses four routinely available clinical variables at diagnosis: Age ECOG performance status Serum lactate dehydrogenase (LDH) level (relative to the upper limit of normal) White blood cell (WBC) count
Risk Groups: Based on these variables, patients are classified into three risk categories:
Low risk: Median overall survival (OS) not reached (5-year OS ~60%)
Intermediate risk: Median OS ~51 months
High risk: Median OS ~29 months
The simplified MIPI is a simplified version (s-MIPI) exists for easier bedside application, showing similar predictive power.
MIPI-c (Combined MIPI): When the Ki-67 proliferation index, a marker of tumor cell proliferation is available, the combined MIPI (MIPI-c) further refines risk stratification into four groups, improving prognostic accuracy.
MIPI is widely used for risk-adapted treatment decisions in MCL, helping to guide therapy intensity and predict outcomes.
Patients with 0 to 3 points in summary were classified as low risk, patients with 4 to 5 points as intermediate risk, and patients with 6 to 11 points as high risk.
The percentage of Ki-67 positive cells was available in 236 lymph node biopsies of the 455 MCL patients with a median of 14.5% and range of 1.2% to 91.0%.
The number of mitoses per square millimeter was counted in 162 cases with a median of 4, range 0 to 72.
Both proliferation parameters showed strong univariate prognostic relevance for OS with an RR of 1.29 for Ki-67 elevated by 10% and 1.27 for the number of mitoses elevated by 10/mm2.
Patients with Ki-67 assessed showed significantly less spleen and bone marrow involvement, better performance status, more involved nodal areas, and larger lymph nodes than patients without available Ki-67.
There is no significant difference in OS of patients with or without data on Ki-67 (median OS 58 and 57 months).
Ki-67 remains independently significant from the MIPI clinical score.
Based on data of 455 patients with advanced stage MCL from 3 randomized trials of GLSG and European MCL Network, a
The MIPI is the first prognostic index specific to MCL patients and, more importantly, allows a clear separation of 3 well-balanced groups of patients with significantly different prognoses.
The methods for the detection of peripheral blood involvement, however, were mostly not adequately described and sensitivity of different methods may vary substantially.
Although peripheral blood involvement may occur without leukocytosis, a high WBC count probably reflects peripheral blood involvement.