Are there risk factors that can predict outcome in multiple myeloma?

This study explored a new method for determining disease risk levels in multiple myeloma. The authors concluded that combining three factors (the ISS score, chromosomal abnormalities, and lactate dehydrogenase levels) offered a clear distinction between three risk groups and their outcomes.

Multiple myeloma is a diverse disease. Survival rates can range from a few months to more than 10 years. A method for accurately predicting risk and outcome is needed.

The International Staging System (ISS) is a method of separating patients by risk. The ISS takes two factors into account: beta2-microglobulin levels (a measure of tumor size and kidney function) and albumin levels (levels decrease with increased inflammatory markers produced by myeloma cells). Overall survival (OS, time from treatment until death from any cause) has been shown to be an average of 62 months for ISS stage I, 44 months for ISS stage II, and 29 months for ISS stage III.

Chromosomal abnormalities (CA, changes in the genetics of a cell) have also been shown to be predictive of outcome. These include the del(17p), t(4;14)(p16;q32), and t(14;16)(q32;q23) abnormalities. Lactate dehydrogenase (LDH) is a marker of cell and tissue damage. High levels can be predictive of outcome. It is not clear if these three factors combined would offer a clearer separation of risk groups and predicted outcome.

This study combined ISS, CA, and LDH levels into one revised risk model (the R-ISS) for multiple myeloma patients. This study combined information from 11 previous trials, including 4,445 patients. 65% of patients were age 65 or younger. 60% of patients were treated with stem cell (immature blood cell) transplantation. Patients were followed for an average of 46 months.

Patients with ISS stage I, no high-risk CA, and normal LDH were considered R-ISS stage I. Patients with ISS stage III, high-risk CA, and high LDH were considered R-ISS stage III. Patients with ISS stage II and all other combinations of CA and LDH were considered R-ISS stage II.

28% of patients were R-ISS stage I. 62% of patients were R-ISS stage II. 10% of patients were R-ISS stage III. In comparison, based on the original ISS, 36% of patients were considered stage I, 37% were stage II, and 22% were stage III (5% of patients had missing data).

Five-year OS was 82% for R-ISS stage I, 62% for R-ISS stage II, and 40% for R-ISS stage III. Five-year progression-free survival rates (time from treatment until disease progression) were 55% for stage I, 36% for stage II, and 24% for stage III.

The risk of death was 32% higher for patients over 65. The risk was 3.59 times higher for stage II compared to stage I. The risk was 9.64 times higher for stage III compared to stage I. The risk of disease progression was 3.37 times higher for stage III compared to stage I. 

This study concluded that the R-ISS was a simple method of separating patients into risk groups predicting prognosis.