MRD Measurement Shows Promise for Making Informed Treatment Decisions in Myeloma

The measurement of minimal residual disease (MRD), the small number of cancer cells in the body after cancer treatment, has the potential to inform treatment decisions for patients with multiple myeloma, according to Dr. Barry Paul.

“(The role of MRD measurement) is an evolving role and one I hope will be pertinent in the future,” Paul, from Levine Cancer Institute, Atrium Health, said during a presentation at CURE’s Educated Patient Summit on Multiple Myeloma, held Dec. 14, in Charlotte, North Carolina.

MRD

MRD is measured using samples from either a blood draw or a bone marrow aspiration through flow cytometry, next-generation sequencing, and imaging tests.

Physicians use MRD to measure the efficacy of cancer treatment and to predict which patients are at risk for relapse. Those who test positive still have cancer cells detected after treatment, while those with a negative biomarker have no disease detected. MRD-negativity can be associated with longer remissions and improved survival rates among patients.

Measurement sensitivity varies, but in general, it is one in 10,000 (10^-4) to one in 1 million cells (10^-6). “What we typically shoot for is less than one in 1,000,000 cells. So, we’ll take bone marrow aspirates and we’ll collect 1 million cells and we hope to find no myeloma cells in those million cells.”

Surrogate Biomarker

A surrogate biomarker is used in therapeutic trials as a substitute for a clinically meaningful endpoint, measuring how a patient feels, functions or survives, to predict the efficacy of the therapy.

Although not approved by the Food and Drug Administration (FDA) as a surrogate biomarker in clinical trials, MRD measurement could help to decrease the time to accrue data points and increase the time it takes for the agency to make a decision on the drug, Paul said. In addition, the surrogate biomarker could inform treatment decisions to determine who may fail or have a superior response earlier.

“Myeloma patients tend to do very well. They have long progression-free and overall survival,” Paul said. “That being said it makes it very challenging for us to evaluate how well a drug is working. So, if we can find surrogate markers, we can get an earlier endpoint. We can know earlier in the treatment cycle whether a patient is getting benefit, or the drug has efficacy, and we should move forward with this drug in the patient.”

However, there is currently no standardized detection method or time point for MRD as a surrogate biomarker. For example, a “cutoff” for MRD improvement from therapy is needed and may vary because of the advances being made with MRD assays.

Prognostic Biomarker

A prognostic biomarker informs physicians about patients’ outcomes, independent of the treatment that was received or its potential benefit and can evolve to be a predictive biomarker. For example, age and cancer stage can be prognostic in that any treatment benefit would be unrelated to their presence or absence.

Essentially, the more negative an MRD measurement is, the better a patient’s prognosis will be.

With current technology, MRD appears to be prognostic, Paul said, but it has not helped to inform treatment decisions as of yet. “It is challenging to incorporate this into a practice outside the context of a clinical trial,” he added.

Predictive Biomarker

A predictive biomarker predicts differential treatment effects based on its presence.

This biomarker is being used in ongoing clinical trials to determine treatment options in the intent-to-treat populations. “This allows us to inform patients and to make informed decisions with patients to make sure we’re getting the right drug to the right patient and we’re not doing more than we need to do. We’re not causing patients undue toxicities or unnecessary costs. We’re doing exactly what the patients need, no more, no less.”