Results from a recent French study identified several factors that predict long-term survival of patients newly diagnosed with multiple myeloma. These prognostic factors include the absence of three key chromosomal abnormalities, low beta-2 microglobulin levels in the blood, and younger age.

The three key chromosomal abnormalities that were absent in patients who survived longer were a gain in chromosome 1 (called 1q gain), a translocation from chromosome 4 to 14 (called t(4;14)), and a deletion in chromosome 17 (called del(17p)). Patients who lived longer were also younger than 55 years of age and had blood beta-2 microglobulin levels below 5.5 mg/L.

“There are several important observations [from this study],” noted Beacon Medical Advisor Dr. Peter Voorhees, an assistant professor of hematology and oncology at the University of North Carolina in Chapel Hill, who was not involved in the study.  “Firstly, this study reaffirms the prognostic importance of gains on the long arm of chromosome 1.  [In addition,] the absence of any high-risk features identifies a group of patients, representing 20 percent of all patients, who have an excellent long-term outcome,” he said.

Based on their findings, the French researchers recommend that 1q gain be added to the panel of risk factors that newly diagnosed myeloma patients are screened for. Both t(4;14) and del(17p) are already on the regular testing panel.

The researchers point out, however, that the patients included in the study did not receive initial treatment with novel agents such as thalidomide ^[5] (Thalomid), Revlimid ^[6] (lenalidomide), or Velcade ^[7] (bortezomib). Other studies have suggested that some novel drugs can overcome poor prognosis associated with certain chromosomal abnormalities.

“Although patients that were included in this analysis received ‘old school’ induction therapy, it stands to reason that the prognostic model that they have developed would be applicable to modern-day therapy,” said Dr. Voorhees. “Patients identified as good risk based on this model should do even better with current therapy,” he added.

Previous studies have shown that the presence of chromosomal abnormalities can have a negative effect on myeloma prognosis (see related Myeloma Beacon ^[8] news).

Elevated levels of beta-2 microglobulin in the blood have also been associated with increased disease severity (see related Myeloma Beacon ^[9] news).

However, the effects of these factors on long-term survival of myeloma patients remain poorly understood because there are very few studies that have followed patients over extended periods of time.

In the current study, the French investigators addressed this problem by retrospectively analyzing genetic and other risk factors in patients who had enrolled in myeloma trials about eight years ago. They then tested if these risk factors could be used to predict long-term survival.

The researchers included 520 patients in their analysis, all of whom had enrolled in two French trials. All patients were younger than 66 years of age and were newly diagnosed with multiple myeloma at the start of the trials.

The trial participants had received induction therapy with vincristine ^[10] (Oncovin), doxorubicin ^[11] (Adriamycin), and dexamethasone ^[12] (Decadron), followed by high-dose melphalan ^[13] (Alkeran) plus stem cell transplantation.

The median follow-up period was about 7.5 years.

The researchers found that older age (above 55 years), higher beta-2 microglobulin levels (above 5.5 mg/L), low red blood cell counts, and deletions in chromosomes 13 and 17, and t(4;14) had a negative effect on progression-free survival.

They also found that older age, higher beta-2 microglobulin levels, t(4;14),del(17p), and 1q gains had a negative effect on overall survival.

According to the researchers, the fact that the 1q gain impacted overall but not progression-free survival suggests that this abnormality becomes more important as the disease progresses.

Taking these risk factors into account, the researchers developed a mathematical model that could predict overall survival based on the number of risk factors a patient carried.

The median overall survival for all study participants was 7.3 years.

Patients without any risk factors (20 percent of the patients included in the analysis) had the longest survival time (not yet reached).

The median overall survival time was 9.5 years for patients with one risk factor (44 percent) and 5.6 years for patients with two risk factors (26 percent).

Patients with more than two of these risk factors (11 percent) had the shortest median overall survival time of less than three years.

Statistical analysis also showed that t(4;14) had the worst impact on overall survival time.

For further information, please see the study in the Journal of Clinical Oncology ^[14] (abstract).