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Combined Index Predicts Early Multiple Myeloma Progression-Related Death in Patients Receiving Front-Line Autologous Stem Cell Transplantation

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Key Points

  • The combined index consists of high LDH level, ISS stage III disease, and presence of t(4;14) and/or del(17p).
  • The index distinguished high- and low-risk groups for 2-year progression-related death and for 2-year overall survival, including overall survival among patients receiving bortezomib-based induction therapy. 

In a European study reported in the Journal of Clinical Oncology, Moreau et al developed and validated a combined index for prognosis in patients with multiple myeloma treated with front-line autologous stem cell transplantation. The index, consisting of high lactate dehydrogenase (LDH) level, International Staging System (ISS) stage III disease, and adverse cytogenetics, identified a group of patients at high risk of early multiple myeloma progression-related death and overall mortality.

Study Details

The index was developed using patient-level data from one clinical trial (Intergroupe Francophone du Myélome 2005-01 trial, N = 482) and validated in populations from three additional trials (Gruppo Italiano Malattie Ematologiche dell’ Adulto 26866138-MMY-3006 trial, N =480; Programa para el Estudio de la Terapéutica en Hemopatía Maligna-GEMMENOS65 trial, N = 390), and Hemato-Oncologie voor Volwassenen Nederland-65/German-Speaking Myeloma Multicenter Group-HD4 trial, N =827).

Index scores were: 0 = absence of any adverse factor; 1 = presence of only one adverse factor from among LDH level higher than normal, ISS stage III disease, and presence of t(4;14) or del(17p); 2 = presence of high LDH and ISS stage III disease in the absence of t(4;14) and del(17p); and 3 = t(4;14) or del(17p) in addition to ISS stage III disease or high LDH.

Progression-Related Death and Overall Survival

In the cohort combining the three validation populations, 56% of patients had an index score of 0, 32% had a score of 1, 4% a score of 2, and 8% a score of 3. Rates of multiple myeloma progression–related death within 2 years from initiation of treatment were 3.7% among patients with a score of 0, 7.7% in those with a score of 1 (estimated odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.2–3.8, vs score of 0), 20.4% among those with a score of 2 (OR = 6.5, 95% CI = 2.8–15.1), and 24.4% among those with a score of 3 (OR = 8.2, 95% CI = 4.4–15.3).

Two-year overall survival among patients in all 4 trials was 93%, 85%, 67%, and 55%, respectively (P < .001 across groups). Among the 855 patients who had received bortezomib (Velcade)-based induction therapy in all four trials, 2-year overall survival was 93%, 86%, 73%, and 52%, respectively (P < .001 across groups).

The investigators concluded, “Our model allows the simple definition of a subgroup of [multiple myeloma] patients at high risk of early [multiple myeloma] progression-related death despite the use of the most modern and effective strategies.”

Philippe Moreau, MD, of University Hospital H?tel Dieu, Nantes, is the corresponding author for the Journal of Clinical Oncology article. 

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®.


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