Minimal residual disease status improved the response evaluation in patients with Waldenström's macroglobulinemia

Wenjie Xiong; Zanzan Wang; Tingyu Wang; Ying Yu; Yanshan Huang; Hao Sun; Jiawen Chen; Rui Lyu; Huijun Wang; Yuting Yan; Qi Wang; Wei Liu; Gang An; Weiwei Sui; Wenyang Huang; Dehui Zou; Zhijian Xiao; Jianxiang Wang; Guifang Ouyang; Lugui Qiu; Shuhua Yi

doi:10.3389/fimmu.2023.1171539

Minimal residual disease status improved the response evaluation in patients with Waldenström's macroglobulinemia

Front Immunol. 2023 May 10:14:1171539. doi: 10.3389/fimmu.2023.1171539. eCollection 2023.

Authors

Wenjie Xiong^{1

2

3}, Zanzan Wang⁴, Tingyu Wang^{1

2

3}, Ying Yu^{1

2

3}, Yanshan Huang^{1

2

3}, Hao Sun^{1

2

3}, Jiawen Chen^{1

2

3}, Rui Lyu^{1

2

3}, Huijun Wang^{1

2

3}, Yuting Yan^{1

2

3}, Qi Wang^{1

2

3}, Wei Liu^{1

2

3}, Gang An^{1

2

3}, Weiwei Sui^{1

2

3}, Wenyang Huang^{1

2

3}, Dehui Zou^{1

2

3}, Zhijian Xiao^{1

2

3}, Jianxiang Wang^{1

2

3}, Guifang Ouyang⁴, Lugui Qiu^{1

2

3}, Shuhua Yi^{1

2

3}

Affiliations

¹ State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
² Department of Lymphma & Myeloma, Haihe Laboratory of Cell Ecosystem, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
³ Tianjin Institutes of Health Science, Tianjin, China.
⁴ Department of Hematology, Ningbo First Hospital, Ningbo, China.

Abstract

Introduction: Minimal residual disease (MRD) has been recognized as an important prognostic factor of survival in patients with hematological malignancies. However, the prognostic value of MRD in Waldenström macroglobulinemia (WM) remains unexplored.

Methods: We analyzed 108 newly diagnosed WM patients receiving systematic therapy and assessed for MRD by multiparameter flow cytometry (MFC) using bone marrow samples.

Results: Of the total patients, 34 (31.5%) achieved undetectable MRD (uMRD). A hemoglobin level of >115 g/L (P=0.03), a serum albumin level of >35 g/L (P=0.01), a β2-MG level of ≤3 mg/L (P=0.03), and a low-risk International Prognostic Scoring System for WM (IPSSWM) stage (P<0.01) were associated with a higher rate of uMRD. Improvements in monoclonal immunoglobulin (P<0.01) and hemoglobin (P=0.03) levels were more evident in uMRD patients compared with that in MRD-positive patients. The 3-year progression-free survival (PFS) was better in uMRD patients compared with that in MRD-positive patients (96.2% vs. 52.8%; P=0.0012). Landmark analysis also showed that uMRD patients had better PFS compared with MRD-positive patients after 6 and 12 months. Patients who achieved partial response (PR) and uMRD had a 3-year PFS of 100%, which was significantly higher than that of patients with MRD-positive PR (62.6%, P=0.029). Multivariate analysis showed that MRD positivity was an independent factor of PFS (HR: 2.55, P=0.03). Moreover, the combination of the 6th International Workshop on WM assessment (IWWM-6 Criteria) and MRD assessment had a higher 3-year AUC compared with the IWWM-6 criteria alone (0.71 vs. 0.67).

Discussion: MRD status assessed by MFC is an independent prognostic factor for PFS in patients with WM, and its determination could improve the precision of response evaluation, especially in patients who achieved PR.

Keywords: Waldenström’s macroglobulinemia; minimal residual disease; multiparameter flow cytometry; prognosis; remission.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Neoplasm, Residual / diagnosis
Prognosis
Progression-Free Survival
Waldenstrom Macroglobulinemia* / diagnosis

Grants and funding

This work was supported by grants from the National Nature Science Foundation of China (81900203, 81970187, 82170193, 82170194 and 81920108006), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2022-I2M-1-022 and 2021-I2M-C&T-B-081).The Lymphoma Research Fund of China Anti-Cancer Association.