Goals of an MRD-Based Discontinuation Trial in Multiple Myeloma

Ben Derman, MD, assistant professor of medicine at the University of Chicago Medical Center, discussed the rationale for an ongoing clinical trial evaluating minimal residual disease (MRD)-guided discontinuation of maintenance therapy in patients with multiple myeloma.

Derman says that MRD negativity status following therapeutic intervention is strongly associated with improved prognosis, and the more sensitive MRD threshold of MRD 10^-6 is associated with better outcomes. Multiple therapies are capable of achieving MRD negative complete responses in patients.

Lenalidomide (Revlimid) is the most common maintenance therapy for multiple myeloma, but it is usually continued indefinitely since there are no studies showing when it is safe to stop treatment. This may be detrimental to patient quality of life since it has toxicities including the risk of developing other cancers and can be extremely expensive for patients, according to Derman.

The prospective MRD2STOP trial (NCT04108624) uses multimodal MRD negativity to determine when maintenance therapy can be discontinued if they are MRD negative by flow cytometry, next-generation sequencing, and PET/CT scans. MRD-negative patients could discontinue lenalidomide maintenance and are monitored for up to 3 years for changes in MRD status, progression-free survival, and overall survival.

TRANSCRIPTION:

0:08 | We presented this oral presentation which we called a prospective trial using multimodal MRD negativity to guide discontinuation of maintenance therapy in myeloma, which we…call MRD2STOP. The idea is based on the fact that MRD…we know it has strongly been associated with improved prognosis in myeloma. More importantly, MRD negativity at a depth of what we call 10^-6 or detecting 1 clonal myeloma cell within a million cells in the bone marrow, we know that that carries superior prognosis over less-sensitive thresholds. So, we've arrived at a good problem in myeloma. We have lots of therapies that can induce and sustain MRD negativity, including maintenance therapy, which involves a single-agent drug, usually lenalidomide. Lenalidomide can convert patients who haven't reached MRD negativity to get there or can sustain that.

1:18 | The problem is, we don't know when to stop lenalidomide, if ever. The standard of care in the United States is generally to continue indefinitely. This impacts quality of life, it can lead to second cancers, which is a major concern for our patients long term, and also it carries significant financial toxicity; the drug can cost $18,000 per month and that price has been rising over the years. The question for this trial came from patients because they were constantly asking us can we stop treatment at some point; is there a way? What we set out to answer is, can this multimodal sustained MRD negativity guide discontinuation of maintenance therapy in myeloma. When I say multimodal, what I mean is using the different tools at our disposal that are actually available in the clinic right now as part of a standard-of-care approach to guide discontinuation.