The International Myeloma Foundation and the EuroFlow Consortium hosted the Second Annual MRD Consortium in Myeloma on October 10, 11, 2016. Held in Salamanca, Spain, this workshop provided a forum for the update and discussion of the recent advances in myeloma minimal residual disease (MRD) monitoring. The meeting specifically focused on the innovative Next Generation Flow (NGF) approach developed through the collaborative work from the Black Swan Research Initiative.

The meeting kicked off with the IMFs Chairman of the Board Dr. Brian Durie and the University of Salamancas Dr. Alberto Orfao welcoming the 124 attendees to this ancient city in northwest Spain. The scale of the event was global, with eager participation from more than 50 institutions representing 25 countries.

The role of MRD in the treatment of myeloma

Dr. Maria-Victoria Mateos (University of Salamanca) set the stage with the first session that outlined all the new myeloma therapies that will potentially help patients achieve MRD-negative status. During this session, Dr. Brian Durie emphasized the central role of precise MRD testing needed to monitor disease at low levels. Dr. Bruno Paiva reiterated this point, echoing that MRD-negative is an endpoint to achieve the best outcomes for myeloma patients.

How does Next Generation Flow work?

The centerpiece of this two-day workshop was Dr. Alberto Orfaos presentation, Next generation flow for high-sensitive MRD monitoring in multiple myeloma: an update. Dr. Orfao explained that the ideal antibody cocktail necessary to detect myeloma has been determined over the past three years of work. This work identified that the 8-color (antibody) 2-tube method is a very robust myeloma detection panel designed to replace the currently used, less sensitive methods.

Since the 2014 Flow Cytometry workshop, questions emerged about these antibodies and the potential of the NGF method. Over the past two years, test centers have discovered a method that is standardized, reproducible, and remarkably sensitive. But there are still many questions that need to be answered. The focus now is on how to adopt the method using the new multidimensional computer software approach that will automatically select myeloma cells within the bone marrow and/or in blood samples.

Powerful automated computer program

Members of the audience literally gasped when Georgian Grigore of the Salamanca research team demonstrated how simple this automated computer program is for NGF. It will produce a complete printout that shows the number of myeloma cells present at a sensitivity level of
10-5 or 10-6, or one myeloma cell in a million cells. Subsequently, attendees took part in hands-on learning about both the antibody methods and computer software again resulting in a series of discussions and breakout groups.

Advantages of NGF in myeloma testing

So what makes this NGF method so valuable? First, it is sensitive and robust. Impressive correlations with both remission duration and myeloma patient survival have validated the standardization of this NGF method. With a confirmed negative reading, the initial study population has experienced zero relapses within the last two years.

The NGF method is also broadly available and cost-efficient, even for busy labs that now have access to the new software program. Exciting new uses of this new flow cytometry method are testing the blood (in addition to the bone marrow) and immune monitoring.

Diagnostic and prognostic value

Using the NGF method to test the blood reveals two important aspects of myeloma: biology at the early MGUS and SMM stages, and biology at the point of relapse. In both MGUS and SMM, myeloma cells can be detected in the blood. The numbers and nature of the cells will prove to be important diagnostic and prognostic factors.

At relapse, for example, from an MRD-negative to an MRD-positive status, myeloma cells can be measured in the blood. Even though testing cannot be switched over to a standalone blood test yet, the need for bone-marrow testing may eventually be reduced.

Not only are testing methods being streamlined with NGF, but immune monitoring is also advantageous with this method. As Dr. Orfao explained, the NGF method can assess a patients immune status as MRD-negative or MRD-positive. While it is known that patients with a MRD-negative status can have a good recovery of immune function, a subset of patients who are MRD-positive may also still have favorable immune features. This subset of patients can do extremely well for many years.

Global potential and next steps

NGF is an excellent test that is both sensitive and robust and has sparked enthusiasm globally to adopt the method. The future holds many ongoing research opportunities for NGF, and patients may soon have easy access to it in the US and around the world.

The IMF extends our gratitude to the research teams in Salamanca and Pamplona, who have worked so hard on this. And thanks, as well, to the IMF team and Prof. Jesus San Miguel, one of the founders of the Black Swan Research Initiative.

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