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. 2014 Jul 10;32(20):2173-80.
doi: 10.1200/JCO.2013.53.0329. Epub 2014 Jun 2.

Combination of international scoring system 3, high lactate dehydrogenase, and t(4;14) and/or del(17p) identifies patients with multiple myeloma (MM) treated with front-line autologous stem-cell transplantation at high risk of early MM progression-related death

Philippe Moreau  1 , Michele Cavo  2 , Pieter Sonneveld  2 , Laura Rosinol  2 , Michel Attal  2 , Annalisa Pezzi  2 , Hartmut Goldschmidt  2 , Juan Jose Lahuerta  2 , Gerald Marit  2 , Antonio Palumbo  2 , Bronno van der Holt  2 , Joan Bladé  2 , Maria Teresa Petrucci  2 , Kai Neben  2 , Jesus san Miguel  2 , Francesca Patriarca  2 , Henk Lokhorst  2 , Elena Zamagni  2 , Cyrille Hulin  2 , Norma Gutierrez  2 , Thierry Facon  2 , Denis Caillot  2 , Lotfi Benboubker  2 , Jean-Luc Harousseau  2 , Xavier Leleu  2 , Hervé Avet-Loiseau  2 , Jean-Yves Mary  2
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Combination of international scoring system 3, high lactate dehydrogenase, and t(4;14) and/or del(17p) identifies patients with multiple myeloma (MM) treated with front-line autologous stem-cell transplantation at high risk of early MM progression-related death

Philippe Moreau et al. J Clin Oncol. .

Abstract

Purpose: To construct and validate among patients with multiple myeloma (MM) who were treated with intensive therapy a prognostic index of early MM progression-related death.

Patients and methods: Patient-level data from the Intergroupe Francophone du Myélome (IFM) 2005-01 trial (N = 482) were used to construct the prognostic index. The event was MM progression-related death within 2 years from treatment initiation. The index was validated using data from three other trials: the Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) 26866138-MMY-3006 trial (N = 480), the Programa para el Estudio de la Terapéutica en Hemopatía Maligna (PETHEMA)-GEMMENOS65 trial (N = 390), and the Hemato-Oncologie voor Volwassenen Nederland (HOVON) -65/German-Speaking Myeloma Multicenter Group (GMMG) -HD4 trial (N = 827).

Results: The risk of early MM progression-related death was related to three independent prognostic variables: lactate dehydrogenase (LDH) higher than than normal, International Staging System 3 (ISS3), and adverse cytogenetics [t(4;14) and/or del(17p)]. These three variables enabled the definition of an ordinal prognostic classification composed of four scores (0 to 3). Patients with a score of 3, defined by the presence of t(4;14) and/or del(17p) in addition to ISS3 and/or high LDH, comprised 5% (20 of 387 patients) to 8% (94 of 1,139 patients) of the patients in the learning and validation samples, respectively, and they had a very poor prognosis. When applied to the population of 855 patients who had received bortezomib-based induction therapy in the four trials, the prognostic classification was also able to segregate patients into four categories, with a very poor prognosis attributed to patients with a score of 3.

Conclusion: Our model allows the simple definition of a subgroup of MM patients at high risk of early MM progression-related death despite the use of the most modern and effective strategies.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
Cumulative incidence of early multiple myeloma progression–related death according to the prognostic classification. (A) Intergroupe Francophone du Myélome (IFM) 2005-01 trial, learning sample; (B) validation trials (Gruppo Italiano Malattie Ematologiche dell' Adulto [GIMEMA], Programa para el Estudio de la Terapéutica en Hemopatía Maligna [PETHEMA], and Hemato-Oncologie voor Volwassenen Nederland/German-Speaking Myeloma Multicenter Group [HOVON/GMMG]).
Fig 2.
Fig 2.
Overall survival for 1,601 patients with lactate dehydrogenase, International Staging System, and cytogenetic data available.
Fig 3.
Fig 3.
Overall survival for patients treated in the bortezomib-based arms of the four phase III randomized trials.
Fig A1.
Fig A1.
(A) Original trial. (B) Validation trial. Mo, months.
See this image and copyright information in PMC

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