Chromosomal Abnormalities And Tumor Load Linked To More Rapid Progression In Smoldering Myeloma Patients
Published: Nov 6, 2013 5:03 pm
German researchers recently reported that certain chromosomal abnormalities in patients' myeloma cells are associated with more rapid progression from smoldering myeloma to active, or symptomatic, multiple myeloma.
Specifically, patients in the study who had the chromosomal abnormalities del(17p), t(4;14), and 1q gain, as well as patients with more chromosomes than normal (hyperdiploidy), experienced shorter times until progression to symptomatic myeloma.
Previous studies have shown that hyperdiploidy positively affects outcomes for patients with symptomatic myeloma. In this study, however, the investigators found that hyperdiploidy negatively affects outcomes for smoldering myeloma patients.
The researchers also confirmed previous research linking measures of tumor load, such as the share of abnormal plasma cells in the bone marrow, to a smoldering myeloma patient's risk of progression.
In the conclusion to their study, the investigators write that chromosomal abnormalities “help identify patients with faster progression to symptomatic myeloma and should be assessed in all patients with smoldering multiple myeloma.”
Chromosomal abnormalities are the result of structural changes in the chromosomes of a patient’s myeloma cells.
These changes may occur through deletions, insertions, duplications, or movement of chromosomal regions. Some patients also have missing or extra copies of entire chromosomes.
When a patient has more than the normal number of chromosomes (23 pairs of chromosomes) in their myeloma cells, they have hyperdiploidy.
Researchers have extensively studied the effects that chromosomal abnormalities have on the course of symptomatic multiple myeloma and the survival of patients with this disease.
Previous studies have shown that certain chromosomal abnormalities – particularly ones called del(17p), t(4;14), and 1q gain – negatively affect the survival of symptomatic myeloma patients (see related Beacon news articles 1 and 2).
On the other hand, hyperdiploidy has been shown to positively affect the survival of treated symptomatic myeloma patients.
According to the investigators of the current study, chromosomal abnormalities have not been as extensively studied in smoldering myeloma patients. One of the few previous studies on the subject was published earlier this year (see related Beacon news).
Smoldering myeloma is a precursor to multiple myeloma in which the patient does not display any of the typical myeloma-related symptoms, such as elevated calcium levels, kidney damage, anemia, or bone lesions. Compared to the general population, smoldering myeloma patients are at a higher risk of developing symptomatic myeloma.
Results from recent studies indicate that the risk of progression from smoldering to symptomatic myeloma is 10 percent per year for the first five years after a smoldering myeloma patient’s diagnosis. This risk reduces to 3 percent per year for the next five years, and to 1 percent per year thereafter. The median time to progression is about five years.
However, the risk of progression varies significantly among patients.
The current standard of care for smoldering myeloma is a ‘watch and wait’ approach, which involves monitoring the patient regularly and beginning treatment only once the disease progresses to symptomatic myeloma. This approach is based on previous evidence that treatment during the smoldering stage of the disease does not have an impact on overall survival, yet exposes patients to chemotherapy – and therefore side effects – for a longer period of time.
Recent studies, however, have begun to show that treatment may delay disease progression and even extend overall survival for certain smoldering myeloma patients at high risk of progressing to myeloma (see related Beacon news articles 1 and 2).
It is therefore important to find reliable ways of determining which smoldering myeloma patients are at high risk for disease progression.
In the current study, the investigators sought to assess whether chromosomal abnormalities play a role in the progression of smoldering myeloma to symptomatic myeloma.
Researchers from the University Hospital of Heidelberg and the German Cancer Research Center in Heidelberg retrospectively analyzed data from 248 patients who were diagnosed with smoldering multiple myeloma between November 2003 and September 2012 at one of their institutions.
The median patient age was 60 years.
None of the patients included in the analysis received treatment before progression to symptomatic multiple myeloma or amyloidosis, a myeloma-related disease in which proteins accumulate in organs such as the heart or kidneys, leading to organ damage.
The study investigators used a technique called interphase fluorescent in situ hybridization (iFISH) to detect and identify chromosomal abnormalities.
The median follow-up time was 3.5 years.
During the course of the study, 33 percent of patients progressed from smoldering myeloma to symptomatic myeloma, 2 percent progressed to amyloidosis, and 2 percent died of causes unrelated to myeloma. The median time to progression was 5.6 years.
The investigators detected chromosomal abnormalities in 91 percent of patients. The most common abnormalities included hyperdiploidy (43 percent of patients), 1q gain (29 percent), t(11;14) (23 percent), del(13q) (20 percent), t(4;14) (9 percent), and del(17p) (6 percent).
The presence of del(17p), t(4;14), gain 1q, and hyperdiploidy had significant negative impacts on time to progression. Patients with hyperdiploidy had a decreased median time to progression of 3.9 years, and time to progression was 3.9 years for patients with gain 1q, 2.9 years for patients with t(4;14), and 2.0 years for patients with del(17p).
In contrast, the chromosomal abnormalities del(13q) and t(11;14) did not have a statistically significant effect on time to progression.
A fifth (20 percent) of patients had high tumor mass, which the investigators defined as having both 10 percent or more of total bone marrow plasma cells and a monoclonal (M) protein level of at least 3 g/dL. All other patients included in the study were defined as having low tumor mass.
Patients with low tumor mass had significantly longer time to progression (9.0 years) than patients with high tumor mass (1.2 years).
A fifth of patients also had a high proportion of cancerous plasma cells in their bone marrow, defined as having greater than 95 percent cancerous bone marrow plasma cells. Time to progression for these patients was also 1.2 years, which was significantly shorter than the 9.0 years for patients with a lower proportion of cancerous bone marrow plasma cells.
Overall, the investigators found that four factors -- a high proportion of cancerous bone marrow plasma cells, high tumor mass, hyperdiploidy, and having one or more high-risk chromosomal abnormalities (del(17p), t(4;14), and gain 1q) -- were independently associated with an increased risk of progression from smoldering to symptomatic myeloma.
For more information, please refer to the study in Journal of Clinical Oncology (abstract).
- Multiple Myeloma Molecular Subtypes Are Already Present In MGUS And Smoldering Myeloma Patients
- Chromosomal Abnormalities May Identify Smoldering Myeloma Patients At Higher Risk of Progression
- Regular Whole-Body MRI Scans May Identify Smoldering Myeloma Patients At High Risk For Progression
- MRI Of The Spine Identifies Smoldering Myeloma Patients At High Risk Of Progressing To Multiple Myeloma
- Study Confirms Higher Progression Risk For Smoldering Myeloma Patients With High Percentage Of Plasma Cells In Bone Marrow