International Journal for Doctor of Medicine and  Medical Students (IJDMMS)

Volume 06, Issue 12.17 , December , 2025

17. Multiple Myeloma: Pathogenesis, Clinical Features, Diagnostic Advances, and Evolving Therapeutic Strategies

1. Dr Turdaliev Samatbek [https://orcid.org/0000-0002-0836-0671]

2. Manal Najeeb

( 1, Teacher, International Medical Faculty, Osh State University; Republic of Kyrgyzstan

2, Student Group 15, 5th Year, International Medical Faculty, Osh State University; Republic of Kyrgyzstan )

Abstract

Multiple myeloma( MM) is a clonal plasma cell malignancy characterized by bone marrow infiltration, monoclonal protein production, and end- organ damage. It accounts for  roughly 10 of hematologic  malice and remains incurable despite significant  remedial advances. Over the last two decades, improved understanding of disease biology, cytogenetics, and the bone marrow medium has transformed diagnosis and management. new agents  similar as proteasome inhibitors, immunomodulatory  medicines, monoclonal antibodies, and cellular therapies have markedly  bettered survival. This composition reviews the current understanding of the pathophysiology, clinical presentation,  individual criteria,  threat position, and treatment modalities of multiple myeloma,  pressing recent advances and ongoing challenges.

Introduction

Multiple myeloma is a malignant plasma cell dyscrasia arising frompost-germinal center B lymphocytes that have undergone  physical hypermutation and immunoglobulin class- switch recombination, resulting in the clonal proliferation of antibody- secreting plasma cells( Rajkumar & Kumar, 2020). The  complaint  generally evolves through well-  honored premalignant and asymptomatic stages, most  specially monoclonal gammopathy of undetermined significance( MGUS) and smoldering multiple myeloma, both of which are characterized by the presence of monoclonal immunoglobulin without overt end- organ damage( Kyle et al., 2018). Longitudinal studies have demonstrated that MGUS progresses to multiple myeloma or related plasma cell disorders at an approximate rate of 1 per year, highlighting the  significance of early identification and surveillance.

Multiple myeloma  generally affects aged adults, with a median age at  opinion ranging between 65 and 70 years, and exhibits a clear  manly predominance( Siegel et al., 2024). Epidemiological data further indicate advanced incidence rates among certain ethnical populations and  individualities with a family history of plasma cell disorders, suggesting a combination of  inheritable susceptibility and environmental influences in disease development. Advancing age contributes significantly to  complaint  threat,  probably due to accretive  inheritable mutations and age- related vulnerable dysregulation.

Clinically, multiple myeloma is defined by the infiltration of clonal plasma cells within the bone marrow, leading to the production of monoclonal immunoglobulin( M- protein) and  posterior organ dysfunction. The hallmark clinical manifestations are classically  epitomized by the CRAB criteria, which include hypercalcemia resulting from increased bone resorption, renal impairment due to light- chain deposit and tubular injury, anemia secondary to bone gist  repression, and lytic bone lesions caused by enhanced osteoclastic  exertion and suppressed osteoblastic function( Dimopoulos et al., 2015). Cases  constantly present with bone pain, fatigue,  intermittent infections, and renal dysfunction, significantly affecting quality of life.

 Although multiple myeloma remains an incurable malignancy, patient  issues have  bettered  mainly over the  once two decades. The  preface of  new  remedial agents, including proteasome impediments, immunomodulatory  medicines, monoclonal antibodies, and cellular  curatives, combined with  threat- acclimated and  personalized treatment strategies, has redounded in  pronounced advancements in progression-free and overall survival. Advances in  individual criteria, early  complaint discovery, and  probative care have further contributed to enhanced  complaint control and dragged  survival,  transubstantiating multiple myeloma into a  habitual, manageable condition for  numerous cases.  

 Materials and Methods

This article is a narrative review based on an extensive and methodical  literature search conducted using major biomedical databases, including PubMed and Google Scholar, along with internationally recognized hematology and oncology guidelines issued by authoritative bodies. Peer- reviewed original research articles, randomized controlled trials, methodical  reviews, meta- analyses, and expert consensus guidelines published  generally between 2010 and 2024 were considered eligible for addition. The hunt strategy employed a combination of Medical Subject Headings( MeSH) terms and free- text keywords, including multiple myeloma, plasma cell dyscrasia, proteasome inhibitors, immunomodulatory  drugs, monoclonal antibodies,  new targeted therapies, and autologous stem cell transplantation. fresh search filters were applied to prioritize  mortal studies and publications in the English language. To ensure comprehensive coverage and minimize the risk of omitting applicable data, the reference lists of selected high- impact  papers and guideline documents were manually reviewed. Emphasis was placed on studies that significantly contributed to the understanding of  complaint pathogenesis,  individual criteria,  threat position, and evolving  remedial strategies in multiple myeloma. The collected literature was critically  rated and synthesized to  give an over- to- date and clinically applicable overview of the  complaint.  

 Results

 Pathogenesis and Disease Biology

 Multiple myeloma arises from a multistep process involving  inheritable abnormalities and interactions with the bone marrow microenvironment. Primary  inheritable events include immunoglobulin heavy- chain( IgH) translocations  similar as t( 11; 14), t( 4; 14), and t( 14; 16), or hyperdiploidy( Fonseca et al., 2009). Secondary events include mutations in KRAS, NRAS, TP53, and MYC dysregulation( Walker et al., 2015).

 Myeloma cells interact with stromal cells via cytokines  similar as interleukin- 6( IL- 6), vascular endothelial growth factor( VEGF), and receptor activator of nuclear factor κB ligand( RANKL), leading to osteoclast activation and osteoblast suppression, explaining the characteristic lytic bone disease( Roodman, 2010).

 Clinical Features

 Patients generally present with

 • Bone pain( especially spine and ribs)

 • Fatigue due to anemia

 • intermittent infections

 • Renal impairment

 • Hypercalcemia- related symptoms

 Extramedullary  complaint and tube cell leukemia represent aggressive variants associated with poor prognosis( Usmani et al., 2012).

Diagnosis is grounded on International Myeloma Working Group( IMWG) criteria, which incorporate biomarkers enabling earlier diagnosis before  unrecoverable organ damage( Rajkumar et al., 2014).

Table 1. Major Drug Classes Used in Multiple Myeloma

Autologous stem cell transplantation (ASCT) remains standard for eligible patients and improves progression-free survival (Attal et al., 2017). Novel therapies such as CAR-T cells targeting BCMA and bispecific antibodies show promising results in relapsed/refractory disease (Munshi et al., 2021).

Discussion

The management of multiple myeloma has evolved from conventional chemotherapy to biologically targeted therapies. Early diagnosis using biomarker-driven criteria allows timely intervention. However, challenges remain, including clonal heterogeneity, drug resistance, and disease relapse. Resource limitations in low- and middle-income countries further complicate management, emphasizing the need for cost-effective strategies and early screening.

Future directions include personalized therapy guided by molecular profiling, minimal residual disease (MRD) monitoring, and expanded use of immunotherapies.

Conclusion

Multiple myeloma is a complex and heterogeneous hematologic malignancy associated with considerable morbidity and mortality, largely due to its multisystem involvement and tendency toward disease relapse. Over recent decades, significant advances in the understanding of disease biology, including genetic heterogeneity, bone marrow microenvironment interactions, and mechanisms of treatment resistance, have fundamentally transformed the clinical management of the disease. The introduction of novel therapeutic agents such as proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and emerging cellular therapies has resulted in substantial improvements in response rates, progression-free survival, and overall survival across diverse patient populations.

Despite these achievements, multiple myeloma remains incurable, and long-term disease control continues to pose a major clinical challenge. Ongoing research efforts focusing on early disease detection, refined risk stratification, and individualized, risk-adapted treatment strategies are essential to optimize outcomes. In addition, the development of durable immunologic control through advanced immunotherapies, minimal residual disease guided treatment approaches, and combination regimens holds promise for achieving deeper and more sustained remissions. Continued translational and clinical research, coupled with equitable access to modern therapies, will be critical in further improving survival, reducing disease-related complications, and enhancing the overall quality of life for patients with multiple myeloma.

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