Multiple myeloma is a type of cancer that originates in the plasma cells, a type of white blood cell found in the bone marrow. These abnormal plasma cells can multiply and accumulate, potentially damaging bones, the immune system, and other organs. Treatment for multiple myeloma typically aims to reduce the number of these cancerous cells in the body. Despite successful initial treatment, a small number of cancer cells can sometimes remain, a condition known as “minimal residual disease.”
Understanding Minimal Residual Disease
Minimal residual disease (MRD) refers to the presence of a very small number of cancer cells that persist in the body after treatment. These cells are often too few to be detected by conventional imaging scans or standard blood tests. If left unaddressed, they can eventually lead to the cancer returning, or relapsing.
When a patient is described as “MRD negative,” it means that highly sensitive tests could not detect any remaining cancer cells. Conversely, an “MRD positive” result indicates that a small number of these residual cancer cells are still present. Achieving an MRD-negative status suggests a deeper response to therapy compared to traditional measures like complete remission, which may still leave behind detectable cancer cells.
Why MRD Matters in Multiple Myeloma
MRD status holds significance for individuals with multiple myeloma. Achieving MRD negativity is strongly associated with improved patient outcomes, including longer periods of progression-free survival. It also correlates with extended overall survival. This deeper level of response suggests a more thorough and lasting impact from treatment.
MRD testing provides a more precise evaluation of how effective a treatment has been compared to older methods that might indicate a complete response even when a small number of cancer cells remain. Research shows that patients who achieve MRD negativity experience deeper and more durable remissions. This prognostic value of MRD negativity has been confirmed across various patient groups, including those eligible or ineligible for transplant, and those with newly diagnosed or relapsed disease.
How MRD is Detected
Detecting minimal residual disease requires advanced laboratory techniques due to the extremely low number of cancer cells present. The two primary methods used for MRD detection in multiple myeloma are next-generation sequencing (NGS) and multiparameter flow cytometry (MFC), also known as next-generation flow (NGF). Both techniques are highly sensitive.
Next-generation sequencing analyzes the unique DNA sequences of myeloma cells, specifically looking for rearrangements in immunoglobulin genes that act as a fingerprint for the cancer cells. This method can detect residual cells by identifying these specific genetic markers. Multiparameter flow cytometry, on the other hand, identifies myeloma cells based on their unique surface proteins, or markers, using multiple fluorescently labeled antibodies. A bone marrow sample is processed, and cells are passed through a laser, allowing for the identification and quantification of any remaining abnormal plasma cells based on their distinct protein expression patterns.
Using MRD to Guide Treatment
Minimal residual disease results are increasingly influencing treatment decisions for multiple myeloma patients. For patients who achieve MRD negativity, particularly those without ultra-high-risk genetic features, there may be discussions about de-escalating therapy or even considering a treatment-free interval. This approach aims to reduce side effects and improve quality of life while maintaining disease control.
Conversely, if a patient remains MRD positive after initial treatment, it may suggest that the current therapy is not fully effective at eradicating all cancer cells. In such cases, clinicians might consider intensifying treatment or switching to alternative therapies to try and achieve an MRD-negative state. MRD testing allows for a more personalized approach to treatment, helping to monitor disease status over time and potentially guiding adjustments to optimize long-term outcomes.