Prognostic Factors

There is significant variation in survival of patients with myeloma; though median survival is 3 years,1 some patients can live longer than 7-10 years.19-22 Several prognostic factors that identify groups of patients with significantly different survival probabilities have been identified, and have become indispensable for patient care and counseling (Table 86.2). These factors are also increasingly used for risk stratification in clinical trials to ensure that treatment arms are truly comparable.

Age, stage, hemoglobin concentration, creatinine, calcium, albumin, immunoglobulin class subtype, and extent of bone marrow involvement are all significant predictors of survival.23-25 However, they add minimal additional prognostic value, once the major independent prognostic factors are known.2627 These include serum ^-microglobulin 02M), bone marrow plasma cell labeling index (PCLI), karyotypic chromosome 13 deletion or hypodiploidy, plasmablastic morphology, lactate dehy-drogenase (LDH), and C-reactive protein (CRP).2428

Table 86.2 Prognostic factors in myeloma

Clinically useful, major prognostic factors

Performance status

Stage (by the ISS staging system)

Cytogenetic studies (conventional cytogenetics and/or interphase FISH)

■ Hypodiploidy

■ t (4;14), t(14;16), or deletion 17p Lactate dehydrogenase Plasmablastic morphology

Plasma cell labeling index (limited availability) Circulating plasma cells (limited availability)

Biologically relevant prognostic factors, with limited clinical utility

Microvessel density

Ras and p53 mutations

Immunophenotyping

Serum IL-6 and soluble IL-6 Receptors

STANDARD CLINICAL AND LABORATORY FACTORS Age

As expected, age has an influence on the outcome of patients with myeloma.2627 In particular, patients younger than 40 years of age have a median survival that exceeds 50 months.29 In a recent cohort study, OS was 41 months in patients less than 70 years of age, compared to 26 months in older patients.1 However, age does not seem to add major prognostic information once the p2M and PCLI are known.27 Age also does not appear to be a significant variable for predicting survival after autotransplantation for myeloma, though age restrictions in the larger randomized transplant trials have been to 60 or 65 years.1516 Retrospective analyses of subsets of older patients transplanted at other large transplant centers suggest that a specific age limit need not be imposed in selecting patients for autolo-gous stem cell transplantation.30

Performance status

Performance status is probably the single most powerful predictor of outcome in myeloma, but its value has not been highlighted in the literature. Kyle and colleagues reported on a study of 1027 consecutive patients with newly diagnosed myeloma seen at the Mayo Clinic, in which performance status of 3-4 (using the ECOG scoring system) had a more adverse impact on outcome than any other single variable including PCLI and p2M.1 One of the reasons performance status is not on the list of many studies evaluating prognosis is that most of these studies use cohorts of patients from clinical trials. Most clinical trials automatically exclude those with performance status 3-4 from participating. In contrast, the study by Kyle et al. included all patients with myeloma seen at the Mayo Clinic between 1985 and 1998, not just patients enrolling in clinical trials. The relative risk of a performance status of 3-4 was 1.9 [95% confidence interval (CI) 1.6-2.4], compared to 1.5 for PCLI (95% CI 1.3-1.7) and (32M (95% CI 1.3-1.8). In that study, which predated the era of new active agents against myeloma, patients with good performance status had a median survival of 36 months, compared to 11 months for those with performance status of 3-4.

Stage

Since 1975, the Durie-Salmon staging system (Table 86.3) has been used to stage multiple myeloma. The median survival is about 5 years for those with stage IA disease and 15 months for those with stage IIIB disease using this system. The Durie-Salmon staging essentially measures tumor burden and is limited in the categorization of bone lesions.2431 Some studies have also failed to confirm the prognostic value of the Durie-Salmon stage.2631 The Durie-Salmon staging largely loses prognostic value once the PCLI and p2M are known.27

Durie-Salmon staging for multiple myeloma

Stage I

All of the following:

Hemoglobin >10 g/dL Serum calcium <12 mg/dL

On radiograph, normal bone structure or solitary bone plasmacytoma only

Low M-component production rates

Urine light-chain M-component on electrophoresis <4 g/24 h

Stage II

Fitting neither Stage I nor III

Stage III

One or more of the following:

Hemoglobin <8.5 g/dL

Serum calcium >12 mg/ dL

Advanced lytic bone lesions

High M-component rates

Urine light-chain M-component on electrophoresis >12 g/24 h

Subclassification

A: Serum creatinine <2 mg/dL

B: Serum creatinine >2 mg/dL

Modified from Durie BG, Salmon SE: A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer 36:842-854,1975; with permission of John Wiley & Sons , Inc.

Table 86.4 International staging system for

multiple myeloma

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