-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

3324 Analysis of Peripheral Blood and Bone Marrow Residual Disease Dynamics during Intensive Treatment and Maintenance in Patients with Multiple Myeloma Included in the GEM12MENOS65 and GEM14MAIN Clinical Trials

Program: Oral and Poster Abstracts
Session: 652. Multiple Myeloma: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Minimal Residual Disease
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Noemi Puig, MD, PhD1, Cristina Agullo2*, Teresa Contreras2*, Bruno Paiva3,4,5*, María T Cedena6*, Laura Rosiñol, MD, PhD7,8,9*, Ramon Garcia-Sanz, MD, PhD10*, Joaquin Martinez-Lopez, MD, PhD11,12,13,14*, Albert Oriol Rocafiguera, MD15*, María-Jesús Blanchard16*, Rafael Ríos, MD, PhD17*, Anna Maria Sureda Balari, MD, PhD18, Miguel Teodoro Hernández Garcia, MD, PhD19*, Javier De La Rubia20,21,22,23*, Felipe De Arriba, MD, PhD24*, Luis Palomera, MD, PhD25*, Valentín Cabañas26*, Maria Belen Inigo Rodriguez27*, José Juan Pérez1*, Sergio Castro1*, Bargay Joan28*, Joan Bladé, MD, PhD29,30*, Juan Jose Lahuerta Palacios14*, Jesús San Miguel, MD, PhD31,32,33,34* and Maria Victoria Mateos, MD, PhD1,31,35,36

1Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), University of Salamanca, Salamanca, Spain
2Biochemistry Department, University Hospital of Salamanca, Salamanca, ESP
3Flow Cytometry Core, Centre for Applied Medical Research (CIMA), Instituto de Investigaciones Sanitarias de Navarra (IdiSNA), Cancer Center Clinica Universidad de Navarra (CCUN), Pamplona, Spain
4Cancer Center Clinica Universidad de Navarra, Centro de Investigación Médica Aplicada (CIMA), IDISNA, CIBER-ONC number CB16/12/00369 and CB16/12/00489, Pamplona, Spain
5Cancer Center Universidad de Navarra (CCUN)., Pamplona, Spain
6University Hospital 12 de octubre, Madrid, Spain
7Amyloidosis and Myeloma Unit, Hospital Clinic, IDIBAPS, Barcelona, Spain
8Amyloidosis and Multiple Myeloma Unit, Department of Hematology, IDIBAPS, Hospital Clinic, Barcelona, Spain
9Hematopoietic Cell Transplantation Unit,, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain
10Hospital Universitario de Salamanca (HUSAL), IBSAL, IBMCC (USAL-CSIC), CIBERONC, Salamanca, Spain
11Hospital 12 De Octubre, CIBERONC, Madrid, ESP
12Department of Hematology, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Complutense University, CNIO, CIBERONC, Madrid, Spain
13Centro Nacional de Investigaciones Oncológicas, Madrid, Spain
14Hospital Universitario 12 de Octubre, CIBER-ONC CB16/12/00369, CNIO, Madrid, Spain
15Institute of Oncology and Josep Carreras Institute, Hospital Germans Trias i Pujol, Badalona, Spain
16Hematology, Hospital Universitario Ramon y Cajal, Madrid, Spain
17Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain
18Hospital Duran i Reynals, Institut d’Investigacio Biomedica de Bellvitge (IDIBELL), Universitat de Barcelona, Barcelona, Spain, Barcelona, Spain
19Hospital Universitario de Canarias, Tenerife, Spain
20Hospital Universitario y Politécnico La Fe, Valencia, Spain
21University Hospital La Fe, Valencia, Spain
22Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
23Hospital Universitario y Politécnico La Fe, Valencia, Spain
24Hospital Morales Meseguer, IMIB-Arrixaca, Universidad de Murcia, Murcia, Spain
25Hospital Clinico Universitario Lozano Blesa, Instituto Investigacion Sanitaria Aragon, Zaragoza, Spain
26Hospital Universitario Virgen de la Arrixaca., Murcia, Spain
27University Hospital San Carlos, Madrid, ESP
28Hospital Son Llazter, Palma de Mallorca, Spain
29Hematology Department, Hospital Clinic, IDIBAPS, Barcelona, Spain
30Hospital Clínic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona and GEM/PETHEMA, Barcelona, Spain
31Centro de Investigacion Biomedica en Red de Cancer (CIBERONC)., Madrid, Spain
32Cancer Center Clinica Universidad de Navarra (CCUN), Centro de Investigacion Medica Aplicada (CIMA), Instituto de Investigacion Sanitaria de Navarra (IdiSNA), CIBER-ONC numbers CB16/12/00369 and CB16/12/00489, Pamplona, Spain
33Hemato-Oncology Program. Cima Universidad de Navarra. IdiSNA., Pamplona, Spain
34Cancer Center Clínica Universidad de Navarra (CCUN), CIMA, CIBERONC, IDISNA, Pamplona, Spain
35University Hospital of Salamanca, Salamanca, Spain
36Institute of Cancer Molecular and Cellular Biology, University Hospital of Salamanca, Salamanca, Spain

Introduction: In patients (pts) with multiple myeloma (MM), analysis of minimal residual disease (MRD) dynamics in bone marrow by Next Generation Flow Cytometry (NGF) has shown that conversion of minimal residual disease (MRD) status modulates the risk of progression. Mass spectrometry measuring low-level monoclonal immunoglobulins has shown potential for Peripheral-blood based Residual Disease (PRD) assessment. In this study, we have analyzed the clinical impact of PRD and MRD dynamics in MM pts receiving intensive treatment as per the GEM2012MENOS65 trial and during maintenance as per the GEM2014MAIN trial.

Patients and Methods: In GEM2012MENOS65 trial, pts received six cycles of VRD-GEM induction, autologous stem cell transplantation conditioned with melphalan or busulfan plus melphalan and consolidation with two cycles of VRD-GEM. Patients achieving at least minimal response were offered to be enrolled in the GEM2014MAIN and randomized to maintenance with lenalidomide and low-dose dexamethasone (Rd) or Rd plus ixazomib for two years; if not reaching MRD negativity at this point, pts received three more years of Rd. PRD dynamics were analyzed separately in each trial by Quantitative Immunoprecipitation Mass Spectrometry with anti IgG/A/M, total k and total l beads using the EXENT® Solution (The Binding Site, part of Thermo Fisher Scientific). MRD was analyzed following the recommendations of the IMWG and according to the Euroflow guidelines. Only those pts with available samples at all the time points analyzed (GEM2012: post-induction, post-ASCT and after-consolidation; GEM014: post-consolidation and after 1 and 2 years of maintenance) were included.

Results: 134 out of the 458 pts enrolled in the GEM2012MENOS65 trial and receiving intensive treatment as per protocol were analyzed. At treatment completion (post-consolidation), PRD and MRD status were associated with almost identical prognostic value: median progression-free survival (mPFS) in PRD- not reached (n.r.) vs 3.98 years in PRD+ cases (p=0.0006) and in MRD- n.r. vs 3.99 years in MRD+ cases (p=0.0001).

When dynamics were analyzed, sustained PRD and MRD negativity was observed in 58 (43.3%) and 44 (33.8%) pts and sustained positivity in 42 (31.2%) and 57 (42.5%) pts, respectively. In 35 (26.1%) and 33 (24.6%) pts, PRD and MRD converted from positive to negative, respectively. Sustained PRD or MRD positivity at the 3 time points analyzed was associated with a significantly shorter PFS (mPFS 4.04 years, p=0.0042 and 3.9 years, p=0.0008, respectively), compared to pts remaining negative or converting from positive to negative, in whom mPFS was not reached (Fig.1A).

109 pts out of the 332 pts enrolled in the GEM2014MAIN trial and receiving maintenance treatment as per protocol were analyzed. At treatment completion (after two years of maintenance), PRD or MRD status were associated with comparable prognostic value: mPFS in PRD- and PRD+ cases n.r. (p=0.0039) and in MRD- cases n.r. vs MRD+ 2.87 years (p<0.0001).

When dynamics were analyzed, sustained PRD and MRD negativity was observed in 68 pts (62.4%) and 61 (55.9%) pts and sustained positivity in 19 (17%) and 19 (17%) cases, respectively. In 17 (15.6%) pts PRD and MRD converted from positive to negative and in 5 (5.6%) and 10 (0.91%) from negative to positive, respectively. Sustained PRD positivity at the 3 time points analyzed was associated with a shorter PFS (p=0.0185), compared to pts who remained PRD- or converted from PRD+ to PRD-, in whom mPFS was not reached. The mPFS in pts remaining MRD- or converting from MRD+ to MRD- was similar and has not been reached yet; the mPFS in pts with sustained MRD positivity at the 3 time points analyzed or converting from MRD- to MRD+ was also similar (2.99 years and 2.88 years, respectively). Interestingly, pts converting from PRD- to PRD+ had a poorer PFS (mPFS of 0.86 years) as compared to patients converting from MRD- to MRD+ (mPFS of 2.28 years) (Fig.1B).

Conclusions: In conclusion, assessment of PRD and MRD dynamics during intensive treatment and maintenance allows to define more precisely the patients’ clinical outcome as compared to the analysis of isolated time points. Reaching MRD or PRD negativity post-consolidation or after 2 years of maintenance is associated with a similar prognostic value, thus highlighting the clinical utility of mass spectrometry as an alternative, non-invasive technique for disease evaluation.

Disclosures: Puig: The Binding Site: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other, Research Funding; Janssen: Consultancy, Honoraria, Other, Research Funding; BMS: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Other, Research Funding; Pfizer: Research Funding. Agullo: The Binding Site: Consultancy, Honoraria, Research Funding. Contreras: The Binding Site: Consultancy, Honoraria. Paiva: Roche Glycart AG: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Research Funding; EngMab: Research Funding; GSK: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Adaptive: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Gilead: Honoraria; Oncopeptides: Honoraria. Cedena: BMS: Honoraria; Abbvie: Honoraria; Janssen: Honoraria. Rosiñol: Janssen: Other: Honoraria for lectures; Bristol Myers Squibb/Celgene: Other: Honoraria for lectures; Amgen: Other: Honoraria for lectures; Sanofi: Other: Honoraria for lectures; Takeda: Other: Honoraria for lectures; GlaxoSmithKline: Other: Honoraria for lectures. Garcia-Sanz: Novartis: Consultancy, Honoraria; Kyowa Kirin: Consultancy; Incyte: Consultancy, Honoraria; Lilly: Consultancy; ADC Therapeutics America: Consultancy; Miltenyi: Consultancy; Ideogen: Consultancy; Eusa Pharma: Honoraria; Gilead/Kite: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Roche: Consultancy, Honoraria; Abbvie: Consultancy; BeiGene: Consultancy, Honoraria, Other: TRAVEL, ACCOMODATIONS, EXPENSES, Speakers Bureau; invivo scribe (IVS): Patents & Royalties; Takeda: Consultancy, Honoraria, Other: TRAVEL, ACCOMODATIONS, EXPENSES, Research Funding, Speakers Bureau. Rocafiguera: Menarini: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Sureda Balari: MSD: Research Funding; Kite: Consultancy, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau. Hernández Garcia: Takeda: Consultancy; BMS/Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Janssen-Cilag: Consultancy, Speakers Bureau; GSK: Consultancy. De La Rubia: GSK: Honoraria, Research Funding, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Pfizer: Speakers Bureau; Sanofi: Speakers Bureau; Takeda: Research Funding; Menarini: Honoraria; BMS: Honoraria; Oncopharm: Honoraria. Cabañas: Janssen: Honoraria; BMS: Honoraria; Sanofi: Honoraria; GlaxoSmithKline: Honoraria; Amgen: Honoraria; Janssen: Consultancy; Sanofi: Consultancy; Amgen: Consultancy. Bladé: Amgen: Other: Honoraria for lectures; Janssen: Other: Honoraria for lectures; Celgene/Bristol Myers Squibb: Other: Honoraria for lectures; Sanofi: Other: Honoraria for lectures. San Miguel: SecuraBio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Haemalogix: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Mateos: BMS-Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Takeda: Honoraria; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria; Stemline: Honoraria, Membership on an entity's Board of Directors or advisory committees; University of Salamanca/Gerencia Regional de Salud de Castilla y León: Current Employment.

See more of: 652. Multiple Myeloma: Clinical and Epidemiological: Poster II
See more of: Oral and Poster Abstracts
Previous Abstract | Next Abstract >>
*signifies non-member of ASH