Minimal Residual Disease

A study was performed in patients with newly diagnosed myeloma who had both bone marrow (NGS) and blood (MS) MRD samples drawn at the same time. MS may provide a useful alternative to bone marrow testing to detect MRD in patients and may even help identify patients at increased risk of early relapse if they are MRD negative but MS positive during maintenance therapy.


Principles of MRD Testing
Benjamin A. Derman, MD University of Chicago Chicago, Illinois

Goals of Multiple Myeloma Therapy
Reduce the amount of M protein (as measured by serum protein electrophoresis) or light chains (as measured via the free light chain test) to the lowest level possible.

Eliminate myeloma cells (as measured via minimal residual disease [MRD] testing).
Improve quality of life with as few treatment side effects as possible.
Provide the longest possible period of response before first relapse.
Prolong overall survival.

Measuring Response to Therapy
ClonoSEQ is an FDA-approved next-generation sequencing (NGS) test to measure MRD in multiple myeloma patients.Palumbo A et al. J Clin Oncol. 2014;32:587. Kumar S et al. Lancet Oncol. 2016;17:e328.Degree (or depth) of response is usually associated with better prognosis.Some patients do well despite never achieving a CR.What is MRD?

Myeloma cell burden
The presence of small amounts of myeloma cells in the body after treatment The most sensitive MRD tests can detect at least 1 myeloma cell out of 1,000,000 cells.
Why should we measure MRD?

Level of sensitivity can be different depending on methodology used (flow cytometry or NGS)
and the number of cells analyzed

Key points from 44 studies analyzed
MRD negativity is associated with longer progressionfree and overall survival.This association stands regardless of disease risk, MRD assay used, sensitivity threshold, disease setting, and conventional disease response.

Blood-Based MRD Testing: Mass Spectrometry
A study was performed in patients with newly diagnosed myeloma who had both bone marrow (NGS) and blood (MS) MRD samples drawn at the same time.

MS may provide a useful alternative to bone marrow testing to detect MRD in patients and may even help identify patients at increased risk of early relapse if they are MRD negative but MS positive during maintenance therapy.
Zajec M et al. Clin Chem. 2020;66:421.In some cases, MS from the blood was able to detect disease when bone marrow testing was not-AND this identified patients who would later have disease progression.
Mass spectrometry (MS) is being evaluated as a method to detect free light chains (FLCs) in the blood as a potentially more sensitive test to detect MRD in patients after therapy.There are several different methods to do this.MRD has been associated with longer progression-free and overall survival to predict lower risk of progression.
MRD response-directed therapy is being assessed in clinical studies to explore how to guide treatment decisions in myeloma.
MRD status is under investigation as an end point in clinical studies helping to expedite new drug approval in myeloma.

More evidence for the benefit of longer duration of Revlimid maintenance in patients who are MRD positive than MRD negative. And evidence of ongoing benefit beyond 2-3 years for patients with
both standard-and high-risk disease.After median follow-up of 14 months, 89% remain on study (5% with PD, 6% withdrew).
MRD resurgence occurred in 13% of patients (2 patients had resurgence of M protein and disease progression).

MRD-guided discontinuation of maintenance may carry significant cost savings.
Responses deepened with each phase of treatment-and were similar in patients with zero, one, or two or more highrisk genetic abnormalities.ASCT increased the rates of MRD negativity following induction therapy, benefitting patients with highest-risk disease features.
Nearly all patients with no or only one high-risk genetic abnormality and confirmed MRD negativity had no disease progression or MRD resurgence since stopping treatment.

MASTER Trial
Newly diagnosed myeloma patients  No matter what your disease state-smoldering, newly diagnosed, or relapsed/ refractory-our mentors have insights and information that can be beneficial to both patients and their caregivers.
Contact the Patient Navigation Center at 888-841-6673 to be connected to a Myeloma Mentor or to learn more.
Need help with travel to a clinical study?
• The MMRF has partnered with the Lazarex Cancer Foundation to help provide more equitable access to clinical studies for multiple myeloma patients • This partnership is one facet of the MMRF's commitment to improve diversity and representation in myeloma clinical studies • MMRF has provided $100,000 over 2 years to Lazarex to fund travel, lodging, and food for patients (and a travel companion) so that they can participate in clinical studies that are appropriate for them • Patients are funded according to income guidelines and will be reimbursed for allowed expenses • For more information on this program and to be connected with Lazarex, call our Patient Navigation Center at 1-888-841-6673 Thank you!
al. Blood Cancer J. 2021;11:19.deepest response after myeloma treatment, including bone marrow MRD and imaging MRD.Flow cytometry and NGS are the two most commonly used marrow MRD tests.Blood-based MRD is under investigation.
Myeloma Mentors ® allows patients and caregivers the opportunity to connect with trained mentors.This is a phone-based program offering an opportunity for a patient and/or caregiver to connect one-on-one with a trained patient and/or caregiver mentor to share his or her patient journeys and experiences.