Chapter 2 – Diagnosis and staging

Contributors: Carlos Fernández de Larrea and Joan Bladé

3 – Prognosis

Prognostic factors may be related to the patient, the tumor clone and/or related to tumor mass:

  • Patient: advanced age and poor performance status (ECOG) are two independent prognostic factors. Survival, particularly those under 60 years, has increased significantly during the last 10 years [15]. Renal function is also consistently associated with a shortened survival [16].
  • Tumor clone: a number of features, such as immature or plasmablastic morphology of plasma cells, proliferative index (S phase) or less than 5% plasma cells that are phenotypically normal in the bone marrow at the time of diagnosis, are associated with worse prognosis [2]. However, the most important prognostic factor is the cytogenetic status, mainly detected by fluorescence in situ hybridization (FISH) (Table 2.7) in isolated CD138 plasma cells. High-risk abnormalities include t(4,14) (p16,q32), t(14,16) (q32, q23), deletion of 17p13, abnormalities of chromosome 1 (1q gains, 1p losses), deletion of chromosome 22, and hypodiploidy. By contrast, the presence of the t(11,14) (q13, q32) or 9, 11 and 17 trisomies, and hyperdiploidy are associated with good or average prognosis [17–19].

Table 2.7 Cytogenetic abnormalities identified in malignant gammopathies.

Adapted from © Nature Publishing Group, 2009. All rights reserved. Fonseca et al [17].

  • Tumor mass: the staging system published in 1975 by Durie and Salmon established a relationship between tumor mass and M-protein through mathematical models and has been widely used (Table 2.8) [20]. The International Staging System (ISS), validated in 10,750 patients, is the most reproducible and easy classification for MM at diagnosis, only requiring two biochemical values: albumin and β2-microglobulin (Table 2.9) [21]. The ISS has recently been revised (R-ISS) to improve risk stratification and combine the most common and reliable prognostic tools: the original ISS, chromosomal abnormalities (CA) and serum LDH level (Table 2.10). CA, detected by interphase fluorescent in situ hybridization (iFISH), is now a key biomarker in MM diagnosis and is a significant predictor of poor prognosis, with the presence of high-risk CA associated with a median overall survival of half that of those with standard risk CA [22]. The IMWG encourages all practitioners treating MM to adopt this revised system.

Table 2.8 Durie and Salmon prognostic staging system.
Stages can be divided depending on serum creatinine: (A) serum creatinine <2 mg/dL; and (B) serum creatinine ≥2 mg/dL. Hb, hemoglobin; IgA/G, immunoglobulin A/G. Adapted from © John Wiley & Sons, Inc, 1975. All rights reserved. Durie and Salmon [20].

Table 2.9 Standard risk factors for MM and the revised International Staging System (R-ISS).

CA, chromosomal abnormalities; iFISH, interphase fluorescent in situ hybridization; LDH, lactate dehydrogenase. Adapted from © American Society of Clinical Oncology, 2015. All rights reserved. Palumbo et al [22].