German researchers recently developed a new system that calculates the risk level of multiple myeloma patients based on patient’s overall health status and other diseases a patient has in addition to myeloma.

Their system, called the Freiburg Comorbidity Index, calculates a patient’s risk level by determining the presence of known risk factors, such as poor overall health and kidney or lung disease.

The researchers found that this index can be used independently to predict progression-free survival and overall survival in myeloma patients.

More importantly, they found that when the Freiburg Comorbidity Index was used in combination with the International Staging System, a widely used risk classification model, they were better able to identify low-risk, intermediate-risk, and high-risk patients.

According to the German researchers, this combined system should be studied further in clinical trials and might be useful for guiding personalize treatment strategies.

Background

Physicians often use risk stratification models to help guide their treatment decisions for patients with multiple myeloma. The most commonly used model, named the International Staging System (ISS), categorizes patients into three stages (I, II, and III) based on their levels of beta-2 microglobulin and albumin in the blood. These levels are elevated in patients with advanced-stage disease.

According to the German researchers, it is important to consider not only the patient’s age but also physical condition and any diseases that the patient has in addition to myeloma when determining the optimal treatment for a patient.

The researchers argue that additional diseases, which are also called comorbidities, are frequently not considered when making treatment decisions.  In addition, comorbidities often exclude patients from participating in clinical trials, which means that study results may not be applicable for patients with comorbidities.

Study Design

The researchers at the University of Freiburg Medical Center in Germany developed a new system, called the Freiburg Comorbidity Index (FCI), to better determine the risk of myeloma patients with comorbidities.

The researchers first identified risk factors that are known to impact overall survival: age, Karnofsky performance score, high blood pressure, diabetes, secondary cancers, pain, and liver, heart, lung, and kidney function. The Karnofsky performance status scale, which quantifies a patient’s well-being, ranges from 100 (perfect health) to 0 (death).

Based on an initial set of data from 127 multiple myeloma patients, the researchers found that only the following factors independently predicted progression-free and overall survival: Karnofsky performance status score of less than 70 percent, moderate or severe lung disease, and an estimated glomerular filtration rate of less than 30 mL/min/1.73 m². The glomerular filtration rate assesses kidney function.

They then set each patient’s FCI score equal to the number of risk factors the patient had, with FCI scores ranging from zero to three.

The researchers then sought to validate the FCI scoring system in a larger patient population.

For this purpose, they analyzed their scoring system in 466 myeloma patients treated at the University of Freiburg Medical Center between 2003 and 2009. The researchers report that baseline patient characteristics of the initial and validation groups, such as age, sex, type of myeloma, and disease stage, were similar.  However, the researchers point out that since they are at a research center, their patients tend to be younger than typical myeloma patients, with a median age of 60 years for the initial group and 62 years for the validation group.

All patients in the validation group received standard chemotherapy or stem cell transplantation, depending on the patient age and health. Patients undergoing transplantation received induction therapy with cyclophosphamide ^[1] (Cytoxan), dexamethasone ^[2] (Decadron), and either thalidomide ^[3] (Thalomid) or Velcade ^[4] (bortezomib). Those who did not undergo transplantation received melphalan ^[5] (Alkeran), prednisone ^[6], and either thalidomide or Velcade.

Study Results

In the initial analysis, the researchers stratified patients into three different risk groups based on the number of risk factors present. The median overall survival for patients with an FCI score of 0 was 118 months, compared to 53 months for patients with an FCI score of 1 and 25 months for patients with an FCI score of 2 or 3.

The researchers observed the same trend in overall survival times in the validation analysis.  The median overall survival for patients with an FCI score of 0 was not yet reached at a median follow-up time of 49 months, compared to 86 months for patients with an FCI score of 1 and 39 months for patients with an FCI score of 2 or 3.

Since patients with an FCI score of 0 had a significantly longer median overall survival time than other patients, the researchers categorized patients with an FCI score of 0 as low-risk and patients with an FCI score of 1, 2, or 3 as high-risk.

In a multivariable analysis that took ISS, type of treatment, and patient age into consideration, FCI represented an independent prognostic factor for progression-free survival and overall survival.

ISS also represented a prognostic factor for overall survival. However, little difference was observed in overall survival for patients in ISS I and II, which led the researchers to speculate whether the inclusion of FCI would help to better classify patient risk.

The combination of FCI scores and ISS staging allowed the researchers to further subdivide the patients.

They separated patients into the following three prognostic groups: low risk (FCI 0 and ISS I or II), intermediate risk (FCI 1, 2, or 3 and ISS I or II, or FCI 0 and ISS III), and high risk (FCI 1, 2, or 3 and ISS III).

The five-year overall survival rate was 85 percent for low-risk, 74 percent for intermediate-risk, and 42 percent for high-risk patients, which the researchers stated was a better categorization of patients than when FCI or ISS were used alone.

For more information, please refer to the study in the journal Clinical Lymphoma Myeloma and Leukemia ^[7] (abstract).