Minimal Residual Disease in Multiple Myeloma: Testing Methods and Prognostic Significance

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• MRD Prognostic Importance
• NGS MRD Testing
• Next-Generation Flow Method
• MRD Sensitivity Levels
• MRD Negativity Goal
• Full Transcript

MRD Prognostic Importance in Multiple Myeloma

Response to treatment serves as a major prognostic factor for multiple myeloma patients. Dr. Nikhil Munshi, MD, emphasizes that measuring minimal residual disease is critically important today. MRD assessment directly impacts patient outcomes in clinical studies. This evaluation is now utilized as an endpoint for therapeutic decision-making in myeloma care.

Next-Generation Sequencing for MRD Testing

Next-generation sequencing represents one of the two primary methods for minimal residual disease evaluation. NGS provides a highly sensitive approach to detecting remaining myeloma cells after treatment. Dr. Nikhil Munshi, MD, explains that this sequencing-based method offers deep analysis of the cancer cell population. Physicians can choose this method based on their comfort and laboratory availability.

Next-Generation Flow Cytometry Method

Next-generation flow cytometry serves as the second major method for MRD assessment in multiple myeloma. This technique provides comparable sensitivity to sequencing-based approaches for detecting residual disease. Dr. Nikhil Munshi, MD, notes that both next-generation sequencing and next-generation flow are very similar in their capabilities. The choice between methods depends on physician preference and institutional resources.

Optimal MRD Sensitivity Levels and Detection

The depth of sensitivity represents a critical component in MRD testing for multiple myeloma. The preferred sensitivity level is 10^-6, which enables detection of one cancer cell in one million normal cells. Dr. Nikhil Munshi, MD, acknowledges that technical limitations sometimes prevent achieving this ideal sensitivity. In general practice, a sensitivity of 10^-5 (one tumor cell in 100,000 cells) is considered acceptable for prognostic evaluation.

Achieving MRD Negativity as Treatment Goal

The primary treatment goal for newly diagnosed multiple myeloma patients is achieving MRD negativity. Dr. Nikhil Munshi, MD, highlights emerging data showing this goal applies equally to relapsed myeloma patients. This objective helps determine the patient's response to therapy and guides treatment duration decisions. During his discussion with Dr. Anton Titov, MD, Dr. Munshi emphasized that MRD status informs how much treatment patients should receive and for how long.

Full Transcript

Dr. Nikhil Munshi, MD: Response to treatment is a major prognostic factor for multiple myeloma. What is the state of the art in the evaluation of multiple myeloma patients for minimal residual disease, and what is the level of MRD that signals the best possible prognosis in multiple myeloma?

As I mentioned, measuring minimal residual disease is very important today for the outcome of various studies, but it is also utilized as an endpoint for therapeutic decision making.

There are two methods: one is a sequencing-based method called next-generation sequencing (NGS), and the second method is next-generation flow. Both are very similar methods; whichever method a physician is comfortable with is acceptable.

The critical component is what you asked: what depth we need. A standard preferred depth is getting 10 to the minus six sensitivity, where we can detect one cell in a million.

However, we know that for various reasons—sometimes technical—we may not be able to get that depth. So what is acceptable as general practice is 10 to the minus five, which is the ability to look at one tumor cell in 100,000. That is acceptable.

I think that is what one has to keep in mind. The goal is to get patients to MRD negativity in the newly diagnosed setting.

We have emerging data that a similar goal is quite applicable even when we treat patients with relapsed myeloma. So we have to keep that in mind as we treat patients: determine their response to therapy, and also determine how long and how much treatment they should be getting.