MRD Negativity: A Key Predictor for Multiple Myeloma Outcomes

The benefits of better therapies in myeloma care also come with a challenge - clinical trials are taking longer to run, slowing future innovation and drug development. If the pattern continues, myeloma patients will find they have fewer treatment options in the future.

Traditionally, clinical trials use endpoints like the length of overall survival (OS) or the number of patients who relapsed at a defined time (progression-free survival or PFS). With better myeloma treatments keeping patients in remission for years, these more common clinical trial endpoints can take 8-15 years to yield results. Patients, researchers and pharmaceutical companies can't wait that long to know if a single drug is effective or not.

New strategies are underway to determine if the detection of Minimal Residual Disease (MRD) is an acceptable, earlier endpoint. A patient who is MRD negative means that no detectable myeloma cells are present in the bone marrow using the most sensitive testing.

Groundbreaking Research: MRD-Negativity Strongly Predicts Better Outcomes

A landmark study published in Blood, in collaboration with the HealthTree Foundation, examined data from eight major clinical trials that included 4,907 patients with newly diagnosed multiple myeloma. The research aimed to determine if achieving MRD negativity at 12 months after beginning treatment could predict longer progression free survival (PFS). Key findings included:

• Patients who reached MRD-negativity at 12 months had a significantly lower risk of disease progression
• A strong correlation existed between the treatment's ability to induce MRD-negativity and its impact on PFS
• The relationship between MRD-negativity and longer PFS was consistent across multiple studies
• In relapsed/refractory multiple myeloma patients, the benefit was even greater, with MRD-negativity leading to a much stronger likelihood of extended PFS

The HealthTree Cure Hub® Registry provided valuable data for this research, emphasizing the crucial role of patient organizations in advancing myeloma research.

FDA Approval Process Underway

The FDA will need to approve MRD as a new clinical trial endpoint. These data were presented to the FDA in May of 2024 and received a 12-0 vote in favor of MRD use from an advisory committee (called an ODAC meeting). The FDA takes committee meeting votes into consideration and has not yet ruled on their decision as of the date of this article.

The FDA is likely to approve MRD as a new clinical trial endpoint for accelerated approval. However, traditional PFS and OS endpoints will still need to be tracked to confirm that MRD testing is an equally validated endpoint.

What Does This Mean for Patients?

The results show that MRD negativity is a valuable early marker of treatment success. If MRD negativity rates are approved as a clinical trial endpoint, it would:

• Change clinical trial designs to provide earlier endpoints
• Speed new drug approvals
• Help personalize treatment decisions by providing additional information about disease response

Understanding MRD in Your Personal Journey

While research studies have associated MRD negativity with better outcomes, it's important to remember that each patient's myeloma journey is unique. Many patients maintain excellent quality of life and disease control for years without achieving MRD negativity. MRD status is one important marker among many that your healthcare team considers when evaluating your overall response to treatment.

If you haven't achieved MRD negativity, this doesn't mean your treatment isn't working or that your prognosis is poor. The goal of treatment is to control the disease and maintain your quality of life, which can be accomplished in many ways. Your doctor will consider multiple factors beyond MRD status when planning your care.

More About MRD Testing

MRD testing is performed on a bone marrow sample, which is analyzed using either Next Generation Sequencing, which tests the bone marrow cell's DNA, or flow cytometry. Both methods can detect a single myeloma cell in a million cells.

Read our comprehensive article, How Groundbreaking Clinical Trials Changed The Way We Use MRD Testing in Multiple Myeloma, to learn more about MRD testing, its role in clinical trials, and how it's being used to advance myeloma treatment. This article explains the different MRD testing methods, current clinical trials using MRD as an endpoint, and what these developments mean for patients.

The MRD Way Forward

The analysis of a significant number of patients across multiple trials shows that achieving MRD negativity at 12 months can predict longer progression-free survival. As myeloma research advances, MRD testing will become essential for determining early treatment effectiveness, always considering the complete picture of each patient's health and response.

By participating in the HealthTree Cure Hub® Registry and connecting your medical records, you can contribute to important research like this that is changing the future of myeloma treatment. Your data helps accelerate discoveries that benefit the entire myeloma community.

Create My Cure Hub Account Today

Sources:

• EVIDENCE meta-analysis: evaluating minimal residual disease as an intermediate clinical end point for multiple myeloma