Validation of Mantle Cell Lymphoma International Prognostic Index in European Mantle Cell Lymphoma Network Trials
The Mantle Cell Lymphoma International Prognostic Index (MIPI) was developed in 2008 as the first prognostic stratification system specific for mantle cell lymphoma (MCL). In a study reported in the Journal of Clinical Oncology, Hoster et al confirmed the validity of MIPI in a cohort of two recently completed randomized trials of the European Mantle Cell Lymphoma Network.
Study Details
The study included data from 958 previously untreated patients with mantle cell lymphoma (median age = 65 years, range = 32–87 years) in the MCL Younger and MCL Elderly trials. Patients had to have mantle cell lymphoma of Ann Arbor stages II to IV and Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
In the MCL Younger trial, patients aged ≤ 65 years suitable for high-dose treatment received six cycles of induction therapy with R-CHOP (rituximab [Rituxan] plus cyclophosphamide, doxorubicin, vincristine, and prednisone) or alternating R-CHOP and R-DHAP (rituximab plus dexamethasone, cytarabine, and cisplatin), followed by high-dose chemoradiation and peripheral blood stem cell transplantation in remission.
In the MCL Elderly trial, patients aged > 60 years not suitable for high-dose therapy received eight cycles of R-CHOP or six cycles of rituximab plus fludarabine and cyclophosphamide, followed by maintenance with rituximab or interferon-alfa in remission.
The two trial populations were pooled to assess the prognostic value of MIPI for overall survival and time to treatment failure. MIPI scores are calculated as the weighted sum of baseline values for age, ECOG performance status, lactate dehydrogenase (LDH) activity (as quotient to the upper limit of normal), and white blood cell (WBC) count.
Performance for Overall Survival
Risk level according to MIPI was low in 33% of patients, intermediate in 32%, and high in 35%. The 5-year overall survival rates in these risk groups were 83%, 63%, and 34% (P < .001). Hazard ratios (HRs) for overall survival were 2.1 (P < .001) for intermediate vs low risk and 2.6 (P < .001) for high vs intermediate risk. All four MIPI factors also had independent prognostic impact, with hazard ratios of 1.6 for 10-year increase in age, 1.9 for ECOG performance status of 2, 2.0 for twofold LDH increase, and 1.9 for 10-fold increase in WBC count (all P < .001).
Performance for Time to Treatment Failure
The 5-year time to treatment failure rates were 59%, 37%, and 22%, for MIPI low, intermediate, and high risk (P <.001), and hazard ratios were 1.6 (P < .001) for intermediate vs low risk and 2.1 (P < .001) for high vs intermediate risk. All MIPI factors had independent prognostic impact, with hazard ratios of 1.5 for 10-year increase in age, 2.1 for ECOG performance status of 2, 1.7 for twofold increase in LDH, and 1.4 for 10-fold increase in WBC count (P < .001 for all except P = .0017 for WBC count).
The validity of MIPI was independent of trial and treatment.
The investigators concluded, “MIPI was prospectively validated in a large [mantle cell lymphoma] patient cohort homogenously treated according to recognized standards. As reflected in current guidelines, MIPI represents a generally applicable prognostic tool to be used in research as well as in clinical routine, and it can help to develop risk-adapted treatment strategies to further improve clinical outcome in [mantle cell lymphoma].”
Eva Hoster, PhD, of University Hospital Munich, is the corresponding author for the Journal of Clinical Oncology article.
For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
