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4694 Measurable Residual Disease and Peripheral Residual Disease to Assess Treatment Response in Real-World Patients with Newly Diagnosed Multiple Myeloma

Program: Oral and Poster Abstracts
Session: 653. Multiple Myeloma: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Measurable Residual Disease
Monday, December 9, 2024, 6:00 PM-8:00 PM

Noemi Puig, PhD1, Panagiotis Malandrakis, MD2*, Cristina Agullo3*, Sergio Castro4*, Teresa Contreras3*, Veronica Gonzalez-Calle, MD, PhD5*, Beatriz Rey-Búa6*, Borja Puertas Martínez7*, Evangelos Terpos, MD, PhD2, Meletios A. Dimopoulos2,8,9,10,11,12,13,14, Maria- Victoria Mateos7,15,16,17 and Efstathios Kastritis, MD2,12,18*

1Hospital Universitario de Salamanca (HUSAL), IBSAL, IBMCC (USAL-CSIC), CIBERONC, Salamanca, Spain, Salamanca, Spain
2Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
3Biochemistry Department, University Hospital of Salamanca, Salamanca, ESP
4Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), University of Salamanca, Salamanca, Spain
5University Hospital of Salamanca/IBSAL/Cancer Research Center-IBMCC (USAL-CSIC), CIBERONC, Salamanca, Salamanca, ESP
6Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca, Salamanca, Spain
7University Hospital of Salamanca, Salamanca, Spain
8Princess Margaret Hospital, Toronto, ON, Canada
9Alexandra General Hospital, Athens, Greece
10General Hospital of Athens-Alexandra, Llisia, Greece
11University of Athens School of Medicine, Athens, Greece
12National and Kapodistrian University of Athens, Athens, Greece
13Hematology and Medical Oncology, Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
14National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece
15Hematology Department, IBSAL-University Hospital of Salamanca. University of Salamanca., Salamanca, Spain
16University of Salamanca, Department of Medicine, Salamanca, Spain
17Salamanca/Instituto de Investigacio´ n Biome´ dica de Salamanca/Centre for Cancer Research Institute of Cancer Molecular and Cellular Biology, Salamanca, Spain
18Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Voula,Athens, AL, Greece

Introduction:

The utility of mass spec to identify the M-protein in serum (the so called peripheral residual disease [PRD]) is being actively investigated in patients (pts) with multiple myeloma (MM) enrolled in clinical trials. However, data regarding its value in real life are scarce. Also, despite its recent acceptance as an early endpoint for accelerated drug approval in MM, very few studies have reported about measurable disease (MRD) in the marrow of pts obtained as part of the routine practice. In this study we have analyzed PRD and MRD in parallel in a cohort of newly diagnosed MM (NDMM) pts treated as per the routine clinical practice, comparing the results of both of them and its respective clinical value.

Methods:

A total of 160 paired serum and bone marrow samples obtained from 88 NDMM pts from the Department of Clinical Therapeutics, Athens, Greece were analyzed. MRD was assessed in bone marrow using Next Generation Flow, using the Euroflow protocol (sensitivity 2x10-6). PRD was analyzed in serum with Quantitative Immunoprecipitation Mass Spec using anti IgG/A/M, total κ and total λ beads and the EXENT® system. Both MRD and PRD were evaluated while on maintenance or during continuous treatment, depending if the patient underwent or not a previous autologous stem cell transplantation (ASCT). SPEP/IFE were carried out as per the center’s protocols.

Results:

Pts were diagnosed between November 2015 and May 2022, half of them were male and the median age at diagnosis was 59 years (16 were 66 and older). The isotype of the M-protein was G/A/D/light chain/non secretory in 44/22/2/16/4 cases (57% kappa, 43% lambda) and ISS and R-ISS distribution (I/II/III) was 53/31/16 and 42/42/16, respectively. Based upon eligibility, 64 pts received induction (triplets in 42, quadruplets in 22), HDM with ASCT, consolidation and lenalidomide-based maintenance and 24 pts received continuous treatment (doublets in 2, triplets in 17 and quadruplets in 5 cases), in both groups until disease progression.

At the time of disease evaluation, 12.5% (19/151) samples were IFE+, 19% (30/161) PRD+ and 26% (41/160) MRD+. Comparing IFE vs PRD, 80% of the results were concordant (125/155) and 20% (30/155) discordant: 12 IFE+/MS- and 18 IFE-/MS+. Whereas the IFE status did not discriminate two groups with different progression-free survival (PFS), both PRD and MRD were able to do so as follows: PRD: HR: 6.49 (95% CI, 1.7-23.7), p=0.004 vs MRD: HR: 9.08 (95% CI, 2.8-28.9), p=0.0002). At a median follow up of 26.8 months, the progression rates for PRD and MRD+ pts were 23.3% vs 24.3%. Indeed, comparing PRD vs MRD, 84.38% of the results were concordant (135/160) and 15.63% (25/160) discordant: 18/160 NGF+/MS- and 7/160 NGF-/MS+. Taking the results of NGF as a reference, the negative and positive predictive values of PRD were 86% and 77%, respectively. Interestingly, among the samples classified as achieving ≥CR according to IMWG criteria, both PRD and MRD further stratified pts with significantly different outcomes (PRD: HR: 7.46 (95%CI 1.31-42.45), p=0.0235 vs MRD: HR: 8.28 (95%CI 1.91-35.73), p=0.0047).

Conclusions:

This study reproduces in real life NDMM pts the results previously obtained about PRD and MRD assessment in clinical trials. PRD and MRD can stratify pts treated as part of the routine practice, not only in the global cohort but also in otherwise IFE negative cases. The comparable prognostic value of PRD and MRD underscores the usefulness of the non-invasive EXENT® system, although further validation in a larger group of real-world pts including more pts and samples is warranted.

Disclosures: Puig: Pfizer, Sanofi, Amgen, BMS, Janssen, Takeda, and The Binding Site: Honoraria; Pfizer, Sanofi, Amgen, BMS-Celgene, Janssen, and Takeda: Consultancy. Agullo: The Binding Site: Honoraria. Contreras: The Binding Site: Honoraria. Gonzalez-Calle: Janssen, GSK, Pfizer, BMS: Consultancy, Other: Travel and accommodation, Speakers Bureau. Terpos: Amgen: Honoraria, Other: Travel expenses, Research Funding; BMS: Honoraria; AstraZeneca: Honoraria, Other: Travel expenses; EUSA Pharma: Honoraria, Other: Travel expenses; GSK: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Menarini/Stemline: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria, Other: Travel expenses, Research Funding; Takeda: Honoraria, Other: Travel expenses, Research Funding; Novartis: Honoraria; Antengene: Honoraria, Research Funding; Swixx: Honoraria. Dimopoulos: REGENERON: Honoraria; BMS: Honoraria; GSK: Honoraria; TAKEDA: Honoraria; SANOFI: Honoraria; MENARINI: Honoraria; AMGEN: Honoraria, Membership on an entity's Board of Directors or advisory committees; JANSSEN: Honoraria; BEIGENE: Honoraria; SWIXX: Honoraria; ASTRA ZENECA: Honoraria. Mateos: BMS/Celgene, Janssen-Cilag, Sanofi, Abbvie, Stemline, Oncopeptides, GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Takeda, Regeneron: Honoraria. Kastritis: Genesis Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Prothena: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria; Sanofi: Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH