A New Prognostic Index (MIPI) for Patients with Advanced Stage Mantle Cell Lymphoma.

On behalf of the German Low Grade Lymphoma Study Group (GLSG) and the European MCL Network.

Background: There is no generally established prognostic classification system for patients with mantle cell lymphoma (MCL), as the International Prognostic Index (IPI) and the Follicular Lymphoma International Prognostic Index (FLIPI) have been developed based on data of patients with diffuse large cell and follicular lymphoma, respectively.

Methods: The data of 455 patients with advanced stage MCL treated first-line within three clinical trials of GLSG and European MCL Network have been analyzed to clarify the prognostic relevance of IPI and FLIPI and to derive a new prognostic index of overall survival (OS). Age, sex, ECOG performance status, Ann Arbor stage, B-symptoms, number of extranodal sites, number of involved nodal areas, tumor size, serum LDH activity, WBC count, platelet count, hemoglobin, albumin, β₂-microglobulin and cell proliferation (Ki-67) were considered as candidate prognostic factors. Statistical methods included Kaplan-Meier estimates and logrank test for the validation of IPI and FLIPI and multiple Cox regression with backward variable selection for the derivation of the new prognostic index.

Results: IPI showed a significant impact on OS, but low-intermediate and high-intermediate risk groups comprised more than two thirds of the patients and were not well separated. According to the FLIPI, only 6% of the patients were classified as low risk and almost two thirds of the patients as high risk, and low and intermediate risk groups were not separated. Four of the candidate prognostic factors were independently associated with OS, namely age, ECOG performance status, LDH and WBC count. The relative risk was 1.42 (95% confidence interval 1.18 to 1.72, p = 0.0002) for an increased age by ten years, 2.01 (1.19 to 3.39, p = 0.0088) for an ECOG greater than one, 1.51 (1.13 to 2.02, p = 0.0059) for a 2 fold elevation of LDH and 2.56 (1.66 to 3.95, p < 0.0001) for a 10 fold increase of WBC count. According to these four parameters, patients could be classified into a low risk (44% of the patients, median OS not reached), an intermediate risk (35%, median OS 51 months), and a high risk group (21%, median OS 29 months).

Discussion: IPI and FLIPI showed only modest prognostic discrimination in our external validation data set of patients with advanced stage MCL. In contrast, age, ECOG performance status, LDH and WBC were identified as independent prognostic factors of OS, and three reasonably sized and well separated risk groups were defined. With four clinical prognostic factors readily determined in clinical routine, our new prognostic index (MIPI) is superior to the IPI. Bootstrap validation confirmed the separation of three risk groups, but external validation is still needed. The MIPI may prove to be an important tool to facilitate risk-adapted treatment decisions for patients with advanced stage MCL.