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2237 Making Clinical Decisions to Change Therapy Using Measurable Residual Disease Improves the Outcome in Multiple Myeloma

Program: Oral and Poster Abstracts
Session: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster II
Hematology Disease Topics & Pathways:
Clinically relevant
Sunday, December 6, 2020, 7:00 AM-3:30 PM

Joaquin Martinez Lopez1*, Rafael Alonso Fernández2*, Sandy W. Wong, MD3, Rafael Rios, MD, PhD4*, Nina Shah, MD5, Maria Teresa Cedena Romero, MD, PhD6,7*, Yanira Ruiz-Heredia8*, Jose M. Sanchez, MD9*, Santiago Barrio Garcia, PhD10*, Thomas Martin III, MD11 and Jeffrey L. Wolf, MD11

1Department of Medicine, Division of Hematology-Oncology, University of Califarnia San Francisco, San Francisco
2Translational Hematology Group, Hospital 12 de Octubre-CNIO, Madrid, Spain
3Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA
4Servicio de Hematología y Hemoterapia, Hospital Universitario Virgen de las Nieves, Granada, Spain
5Associate Professor of Medicine, University of California San Francisco, San Francisco, CA
6Hospital 12 de Octubre, Madrid, Spain
7Department of Hematology, Hospital Universitario 12 de Octubre, CNIO, Madrid, Spain
8Hematology, Hospital Universitario 12 de Octubre, CNIO, Complutense, Madrid, Spain
9Hospital 12 de Octubre, Madrid, ESP
10Hematology, Hospital 12 de Octubre. CNIO, Madrid, Spain
11University of California, San Francisco, San Francisco, CA


Measurable residual disease (MRD) testing in multiple myeloma (MM) is increasingly being utilized in clinical trials for the assessment of disease response and as a prognostic tool for predicting response duration. However, there is only limited evidence to date for the use of MRD to make clinical decisions, a serious barrier to its potentially important role in the management of MM patients. This retrospective review analyzes the results of making clinical decisions to change therapy based on MRD assessments in MM patients.


We reviewed 373 patients with MM from 3 health centers through a retrospective search. Patients included in the study had at least one MRD assessment. Clinical decisions to change therapy based on MRD were made in 3 directions: 1. Stop or reduce treatment after MRD negative results; 2. Increase intensity of treatment after MRD positive results; 3. Start a new treatment line after MRD positive results. We gathered all the available data on clinical and biological parameters, induction treatment and response monitoring. MRD was assessed by flow cytometry or next-generation sequencing (Clonoseq) with sensitivity from 10-5to 10-6Statistical analyses were performed with SPSS software version 21.0 (SPSS, Inc., IBM, Armonk, NY).


In 58 out of 373 (16%) patients a clinical decision to change therapy was made. Treatment was reduced or stopped in 24 cases (group 1). Intensity of treatment was increased in 20 cases(group 2) and a new treatment was started in 13cases(group 3). Most of these decisions were implemented during the post-ASCT maintenancephase, although in 3 cases ASCT was avoided based on the MRD result.

For all 373 patients, the median progression-free survival (PFS) was 80 months. Of the 58 cases where a clinical decision was made to change therapy, 33 cases were MRD positive and 25 were MRD negative at the time the decisions were made. 33 patients in this group either remained MRD negative or eventually achieved MRD negativity.

Patients in which a clinical decision was made to change therapy based on MRD (n=58) had a prolonged progression free survival versus those in which therapy remained the same (n=312) (median PFS 97 vs. 75 months, p=0.006) (Figure 1). Moreover, we once again confirmed that patients who achieve MRD negativity demonstrate a prolonged PFS vs those who don’t achieve negativity (median PFS 97 vs. 57 months, p=0.0001).


Clinical decision-making to change therapy based on MRD in MM patients can improve patient outcomes. These results support the integration of MRD assessment in the management of MM patients.

Disclosures: Wong: GSK: Research Funding; Janssen: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; Roche: Research Funding; Fortis: Research Funding; Bristol Myers Squibb: Research Funding. Shah: GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy; BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding. Barrio Garcia: Altum sequencing: Current Employment. Martin: GSK: Consultancy; Sanofi: Research Funding; AMGEN: Research Funding; Seattle Genetics: Research Funding; Janssen: Research Funding. Wolf: Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

*signifies non-member of ASH