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<p>Anaemia affects approximately 73% of multiple myeloma (MM) patients and serves as an independent predictor of reduced quality of life and poor survival. This review synthesizes recent advances in understanding the multifactorial aetiology of MM-associated anaemia, emphasizing the central role of a dysregulated bone marrow microenvironment. Key mechanisms include (a) cytokine network imbalances that serve as central initiating and perpetuating events, impairing erythroid differentiation via GATA-1 suppression; (b) inadequate compensatory erythropoietin (EPO) production despite hypoxia; (c) malignant plasma cell cytotoxicity through Fas-L/TRAIL-mediated apoptosis of erythroid progenitors; and (d) hepcidin-driven iron restriction via BMP/IL-6 signalling in hepatocytes. Building on these pathophysiologic insights, we then present a structured therapeutic framework, operationalized through a target mapping table that systematically catalogues a hierarchy of therapies, providing a translational roadmap from mechanism to individualized treatment. We critically evaluate anaemia management strategies, including conventional approaches, such as erythropoiesis-stimulating agents (ESAs), iron supplementation, and transfusion. These limitations may signal microenvironment-driven anaemia and guide targeted intervention. At the foundation are tumour‑clearing strategies, where anti‑CD38 antibodies exemplify how deep remission drives haematopoietic recovery. BCMA-directed CAR‑T cells and bispecific antibodies (BsAbs), while capable of purifying the microenvironment, introduce a therapeutic paradox. Their potent antimyeloma effect is frequently accompanied by immune effector cell‑associated haematotoxicity, including significant anaemia. Next are strategies that block erythropoiesis‑suppressive signals, notably those targeting the CCL3/p38/GATA‑1 axis and hepcidin overexpression. Further downstream lie approaches aimed at restoring the erythroid niche. Individualized, biomarker‑driven strategies targeting the dominant microenvironmental defect offer a pathway toward durable correction of anaemia in MM patients while controlling disease progression.</p>

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Anaemia in multiple myeloma: evolving insights into bone marrow microenvironment-driven pathogenesis and targeted management

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月22日

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  • Pan Li,
  • Hui Xie,
  • Yanqiang Ji,
  • Fusheng Zhang,
  • Jie Tan,
  • Zheren Chen

摘要

Anaemia affects approximately 73% of multiple myeloma (MM) patients and serves as an independent predictor of reduced quality of life and poor survival. This review synthesizes recent advances in understanding the multifactorial aetiology of MM-associated anaemia, emphasizing the central role of a dysregulated bone marrow microenvironment. Key mechanisms include (a) cytokine network imbalances that serve as central initiating and perpetuating events, impairing erythroid differentiation via GATA-1 suppression; (b) inadequate compensatory erythropoietin (EPO) production despite hypoxia; (c) malignant plasma cell cytotoxicity through Fas-L/TRAIL-mediated apoptosis of erythroid progenitors; and (d) hepcidin-driven iron restriction via BMP/IL-6 signalling in hepatocytes. Building on these pathophysiologic insights, we then present a structured therapeutic framework, operationalized through a target mapping table that systematically catalogues a hierarchy of therapies, providing a translational roadmap from mechanism to individualized treatment. We critically evaluate anaemia management strategies, including conventional approaches, such as erythropoiesis-stimulating agents (ESAs), iron supplementation, and transfusion. These limitations may signal microenvironment-driven anaemia and guide targeted intervention. At the foundation are tumour‑clearing strategies, where anti‑CD38 antibodies exemplify how deep remission drives haematopoietic recovery. BCMA-directed CAR‑T cells and bispecific antibodies (BsAbs), while capable of purifying the microenvironment, introduce a therapeutic paradox. Their potent antimyeloma effect is frequently accompanied by immune effector cell‑associated haematotoxicity, including significant anaemia. Next are strategies that block erythropoiesis‑suppressive signals, notably those targeting the CCL3/p38/GATA‑1 axis and hepcidin overexpression. Further downstream lie approaches aimed at restoring the erythroid niche. Individualized, biomarker‑driven strategies targeting the dominant microenvironmental defect offer a pathway toward durable correction of anaemia in MM patients while controlling disease progression.