2017 Advances in Minimal Residual Disease (MRD) Testing in Multiple Myeloma

On June 16 2017, the MMRF and Memorial Sloan Kettering Cancer Center (MSKCC) co-hosted the Advances in Minimal Residual Disease (MRD) Testing in Multiple Myeloma meeting. This meeting, the fourth in the series, brought together 70 representatives from the MMRF, academia, the pharmaceutical industry, and government agencies to discuss progress in the last year toward standardization and validation of different methods of MRD testing, and approval of MRD testing by the US FDA as an approved measurement and endpoint in clinical trials.

Since the group last convened in 2016, participants published a white paper in the scientific journal Cancer Research, summarizing the state of the science in MRD and critical future directions, both toward validating MRD as a clinical endpoint, and with the goal of eventually incorporating the measurement of MRD into standard practice in the treatment of MM.

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Welcome and Introductions—Presenters:  Ola Landgren & Daniel Auclair

Session I – MRD and Clinical Outcomes in Clinical Trial

MRD in Newly Diagnosed Myeloma–Presenter: Herve Avet-Loiseau (01_915-930)
MRD in Relapsed/Refractory Myeloma—Presenter: Herve Avet-Loiseau (02_930-945)
MRD in Smoldering Myeloma—Presenter: Ola Landgren (MM1Y740TT  D3)

Session II – MRD for Clinical Decision Making in My Myeloma Clinic Today and Tomorrow
Presenter: Faith Davies (Davies_04_NY)
Presenter: Sergio Giralt (05_Giral tMRD in clinic)
Presenter: Andrzej Jakubowiak (06_1050-1100_Jakubowiak)
Presenter:  Ravi ViJ (07_Session 2 – 1100-1110Vij)

Lunch – Fireside Chat—Presenter: Gideon Blumenthal

Session III – Evolving Technologies in Myeloma
VDJ Targeted NGS Adaptive 2.0–Presenter:  Harlan Robbins (08-Robbins-1210. . . )
Invivo Scribe–Presenter:  Maria Arcila (09-Arcila-1220 . . . )
Circulating Tumor Cells and Nucleic Acids ctDNA/RNA Sequencing Based Approaches –Presenter:  Trevor Pugh (10-1230 Pugh-MM-. . . )
CMMS Sequencing—Presenter:  Presenter: Jens Lohr 11-Lohr-1250 . . . )
CMMS–Presenter: Mark Connelly (12-100-110 20170616 .. .)

Proteomics: MALDI Approaches
Presenter:  David Murray (13-session 3 110-130b . . . )
Presenter:  Katie Thoren  (14_Session 3 – 110-13B-Presmmr. . . )

3rd Generation Flow Cytometry and Sequencing Based Proteomics
Presenter:  Ola Landgren (15-Session  3 – 155-215 Landgren)

Host Immune Monitoring
Flow Cytometry–Presenter:  David J. Chung (16-215 MRF 2017. . . )
Neo-Antigens, T-cell Repertories–Presenter:  Alexander Lesokhin (17-225 MM . . . )

PET CT–Presenter:  Neeta Pandit-Taskar (18-pandit-Taskar-235. . . )
DWI MRI–Presenter:  Jens Hillengass (19-Session 3-245-255-Hillengass. . . )

Session IV – Latest FDA Developments and Perspectives on MRD in Myeloma
FDA Perspective on MRD in Myeloma: Today, Tomorrow and Next Steps–Presenter:  Nicole Gormley (20-Session 4-310-325 Gormley . . . )
Development of MRD Wet Labs at the Regulatory Agency–Presenter:  Dickran Kazandjian (21-session 4. . . )

Roundtable Discussion: Already Time for New Updated MRD Guidelines in Myeloma, Why/Why Not?

Lead Host: Ola Landgren

Nicole Gormley
Dickran Kazandjian
Suzanne Lentzsch

This meeting focused on the following key areas:

    • In several large ongoing clinical trials either in the smoldering, newly diagnosed (DFCI IFM) or relapse setting (CASTOR, POLLUX), results showed that achieving MRD negativity (fewer than 1 multiple myeloma cell found in 1 million bone marrow cells) was correlated with a longer period of disease remission before relapse occurs, , regardless of what drug combination the patients received. These studies are showing that depth of response is most critical, rather than how one gets to those MRD negative deeper responses.
    • The experience of clinicians using MRD testing for their patients differed. Some doctors measured MRD in every patient, and it was covered by insurance. Others used MRD measurement rarely, and the test was not always covered by insurance. The panel concluded that MRD is not used frequently in clinical practice despite its prognostic value, pointing to the need to increase efforts to gain approval for this important test to improve outcomes for MM patients. There was also significant discussion on the need for data to guide what clinicians should do if a patient suddenly changes from MRD negative to MRD positive. Does that alone indicate treatment should be changed? What about if a patient is on a clinical trial? Discussion around these points underscored the need for generating additional data to resolve these issues.
    • While the standard approaches for MRD testing involve analyzing bone marrow aspirates from patients, data presented on a number of MRD imaging approaches as well as on blood-based biopsies (where patients’ blood is used to test for MRD measurement as opposed to their bone marrow) showed that new options may soon be available to augment or someday replace the bone marrow aspirate.
    • The FDA continues to express eagerness to work with the MMRF and the MM community on making MRD a clinical trial endpoint. In order to do so, a collaborative effort with the Agency is needed, to evaluate data from ongoing trials to validate MRD in MM along the lines of what has been successfully achieved in breast cancer and in follicular lymphoma.

At the conclusion of the meeting, the group collectively decided that an effort to compile data from ongoing clinical trials which evaluated MRD should be immediately undertaken. This data will be provided to the FDA as soon as possible, with the goal to achieve approval for MRD testing as a new clinical trials endpoint within a year.