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4713 Minimal Residual Disease (MRD) Status and Its Impact on Clinical Outcome Is Highly Variable in Multiple Myeloma and Dependent on Molecular Subgroups Defined By Gene Expression Profiling (GEP)

Program: Oral and Poster Abstracts
Session: 653. Multiple Myeloma: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, Clinical Practice (Health Services and Quality), Clinical Research, Plasma Cell Disorders, Diseases, Lymphoid Malignancies, Survivorship
Monday, December 9, 2024, 6:00 PM-8:00 PM

Sharmilan Thanendrarajan, MD1, Phil Farmer2*, Clyde Bailey, BS1*, Carolina Schinke, MD1, Samer Al Hadidi, MD, MSc3, Maurizio Zangari, MD1, Stephanie Rogers, MNSc, APRN, AGPNP-BC1*, Anne Williams, APRN, MNSc, FNP-C1*, Fenghuang Zhan, MD1, John D Shaughnessy, Jr, PhD4*, Tanvi H. Patel, MD1*, Anup Kumar Trikannad, MD5, Asis Shrestha, MD1*, Syed Naqvi, MD2*, Hira Imad Cheema, MD1*, Trilok Shrivastava, MD1*, Manozna Karri, MD1*, Ramya Bachu, MD1* and Frits van Rhee, MD, PhD1

1Myeloma Center, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR
2Myeloma Center, Winthrop P. Rockefeller Cancer Institute, University of Arkansas For Medical Sciences, Little Rock, AR
3University of Arkansas for Medical Sciences, Little Rock, AR
4Myeloma Center, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical sciences, Little Rock, AR
5Myeloma Center, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, LITTLE ROCK, AR

Introduction:

MRD status has a significant impact on the clinical outcome of patients with multiple myeloma. Achieving sustaining MRD-negative status is considered prognostically relevant for multiple myeloma patients and is highly associated with improved survival. However, the clinical impact of MRD-positive patients and non-sustaining MRD negative patients have not been explored in detail. In this study, we investigate the clinical impact of achieving MRD-positive, sustaining MRD-negative and non-sustaining MRD negative status in multiple myeloma patients after prior treatment depending on their genetic risk profile using gene expression profile (GEP) including seven molecular subgroups (CD-1, CD-2, HY, LB, MF, MS ,PR). In our previous studies we have demonstrated that patients in the HY, CD-1, CD-2 and LB molecular subgroups defined by GEP had superior event free and overall survival compared to the PR, MS and MF molecular subgroup patients differentiating between low-risk and high-risk patients.

Methods:

We included in this single-center retrospective study newly diagnosed multiple myeloma patients after induction chemotherapy and first melphalan based autologous stem cell transplantation (ASCT) with a least two serial 8-color MRD flow cytometry tests with sensitivity at 10-5 within a 1- year window after 2 years of ASCT with available gene expression profile data. Multiple myeloma patients who had two or more serial MRD-negative tests in that time frame were considered as sustaining MRD-negative (SMRD-N) patients, patients without any MRD-negative status at all were considered positive (MRD-P), and patients with at least one MRD-negative test were considered non-sustaining negative (NSMRD-N).

Results:

In our study, we identified 331 MRD-P (35.5%), 223 NSMRD-N (23.9%), and 378 SMRD-N (40.6%) multiple myeloma patients with 932 patients in total. The median predicted overall survival rate was 6.54 years in the MRD-P group, 11.39 years in the NSMRD-N group and not reached yet in the SMRD-N group (p<0.0001). According to our GEP data, all 932 myeloma patients were assigned to different molecular subgroups, as following: HY: 321 (34.4%), CD-2: 173 (18.6%), PR: 118 (12.7%), LB: 107 (11.5%), MS: 88 (9.4%), CD-1: 64% (6.9%), MF: 61 (6.6%). The most frequently noticed MRD status is SMRD-N, as seen in the CD-1, MS, LB, PR, and HY molecular subgroup (7.4, 11.1%, 11.4%, 12.7%, 39.7%, n=28-150). In the MF and CD-2 molecular subgroups the most commonly noticed MRD status is MRD-P with 41% (n=25) and 46.2% (n=80), respectively. NSMRD-N was the least frequently observed MRD status in all molecular subgroups (7.2 – 34.1%, n=16-76), except CD-1 molecular subgroup with equal findings between MRD-P and NSMRD-N at 5.5% and 8.1% (n=both 18). The worst predicted overall survival for the SMRD-N patients is observed in CD-1 molecular subgroup with a median overall survival of 10.5 years, compared to other groups where it is not reached yet. In the MRD-P myeloma patients, there is a significant separation of the clinical outcome between different genetic molecular subgroups. While myeloma MRD-P patients in the PR and MF molecular subgroup have inferior predicted overall survival with a median predicted overall survival with 3.58 and 4.61 years, respectively, myeloma patients in the MS, LB, HY, CD-2, and CD1 molecular subgroup have a relatively better outcome with median predicted overall survival between 6.0 years – not reached yet (p<0.0001). Patients with NSMRD-N status reveal significant differences in clinical outcome. While the 7.5 year predicted overall survival is superior in myeloma patients with CD-2, CD-1, HY molecular subgroup with 81%, myeloma patients in the LB, MS and MF molecular reveal an intermediate predicted overall survival rate with 62% and worse clinical outcome is noticed in the PR molecular subgroup with 38%. (p=0.0002%).

Conclusion:

The MRD status has significant impact on the clinical outcome in multiple myeloma patients. SMRD-N, NS-MRD-N and MRD-P patients have very distinct and specific clinical outcomes depending on their risk profile defined by GEP.

Disclosures: Schinke: Cancer Network: Honoraria; OncLive: Honoraria; Arcellx: Consultancy; Pfizer: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau. Al Hadidi: Sanofi: Consultancy; Pfizer: Consultancy; Janssen: Consultancy. Zangari: Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees. van Rhee: Takeda: Consultancy; Bristol Myers Squibb: Research Funding; Adicet Bio: Membership on an entity's Board of Directors or advisory committees; Castleman Disease Collaborative Network: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Secura Bio: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees; EUSA Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH