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1932 Clinical Implications of Residual Immunophenotypically Normal Plasma Cells within Bone Marrow at Various Disease Stages in Multiple Myeloma

Program: Oral and Poster Abstracts
Session: 653. Multiple Myeloma: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical Research, Real-world evidence
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Wenqiang Yan1*, Lihui Shi2*, Jingyu Xu3*, Lingna Li4*, Jian Cui5*, Chenxing DU3*, Tengteng Yu6*, Shuaishuai Zhang, MD6*, Rui Lv7*, Weiwei Sui, MD3*, Shuhui Deng8*, Yan Xu, MD9*, Dehui Zou3*, Lu-Gui Qiu, M.D.3, Mu Hao, MD3* and Gang An3*

1State Key Laboratory of Experimental Hematology, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood, TIANJIN, China
2State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical Colleg, Tianjin, Tianjin, China
3State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology& Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
4State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical Colleg, Tianjin, CHN
5State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, TIANJIN, China
6State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
7State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences&Peking Union Medical College, Tianjin, CHN
8State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical Colleg, Brookline, MA
9State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Boston, MA

Introduction

Residual normal plasma cells (NPCs) within bone marrow (BM) act as competitors of abnormal plasma cells, playing an important clinical role during the malignant transformation and disease aggressiveness in plasma cell disorders. Previous studies have described the relationship between the persistence of NPCs and survival outcomes at several timepoints, but its clinical significance remain to be fully elucidated across various disease courses. Following the clearance of tumor plasma cells post-treatment, the numerical or proportional alterations in NPCs during the minimal residual disease (MRD) phase could also indicate the evolution of response depth and changes in the immune microenvironment. To date, however, there has been a scarce of research specifically addressing residual NPCs at the MRD stage.

Methods

In light of this, we conducted a comprehensive retrospective study utilizing a substantial flow cytometry dataset comprising 1363 MM patients and nearly 5000 MRD samples across all disease courses from the National Longitudinal Cohort of Hematological Diseases in China (NICHE, NCT04645199).

Results

Our results revealed that 47 (4.5%) newly diagnosed myeloma patients with high NPC ratio (≥5%) within bone marrow (BM) exhibited distinct indolent features, characterized by lower tumor burden, reduced frequencies of cytopenia, immunoparesis, and high-risk cytogenetics. Importantly, high residual NPC ratio at diagnosis or relapse was independently associated with favorable survival outcomes. Furthermore, high absolute level of NPCs at undetectable MRD timepoint was also related with superior clinical benefit and immune reconstitution. Among MRD-positive patients, NPCs ratio within BMPCs was significantly negatively correlated with residual tumor cell levels post-treatment. In addition to MRD status, grouping based on NPC ratio (< 50%, 50-90%, ≥90%) at MRD phase demonstrated better risk stratification for detectable MRD patients compared to residual tumor log levels. The dynamic NPC ratio time-dependent model could classify patients into three groups with diverse longitudinal change trends, which lead to distinct survival outcomes.

Conclusions

Collectively, the persistence of residual NPCS serves not only as a valuable complementary biomarker for risk stratification but also provides valuable insights on reclassifications and kinetics of MRD.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH