Multiple myeloma

Understanding Multiple Myeloma: A Plasma Cell Malignancy

Multiple myeloma, also known as Kahler's disease, is a hematologic cancer characterized by the clonal proliferation of malignant plasma cells within the bone marrow. These abnormal cells produce monoclonal immunoglobulins, or M-proteins, which can be detected in the blood or urine and contribute to organ damage. As the second most common blood cancer after non-Hodgkin lymphoma, multiple myeloma remains incurable but highly treatable, with significant advances in therapy extending survival and improving quality of life.

Pathogenesis and Risk Factors

Multiple myeloma arises from post-germinal center B cells that have undergone somatic hypermutation and class-switch recombination. Genetic abnormalities commonly associated with the disease include translocations involving the immunoglobulin heavy chain locus (e.g., t(11;14), t(4;14), t(14;16)), hyperdiploidy, and chromosomal deletions such as del(17p). Risk factors include age (most patients are over 65), male sex, African ancestry, a history of monoclonal gammopathy of undetermined significance (MGUS), and exposure to radiation or certain chemicals. The disease is preceded by precursor stages such as MGUS and smoldering myeloma.

Clinical Presentation and Diagnosis

The hallmark features of multiple myeloma are summarized by the CRAB criteria: hyperCalcemia, Renal impairment, Anemia, and Bone lesions. Patients may present with bone pain, fatigue, recurrent infections, or renal dysfunction. Diagnosis involves a combination of laboratory studies (serum protein electrophoresis, immunofixation, free light chain assay), bone marrow biopsy, and imaging studies (skeletal survey, MRI, or PET/CT). The International Myeloma Working Group (IMWG) criteria incorporate both clinical symptoms and biomarkers for defining active disease.

Staging and Prognosis

Staging of multiple myeloma traditionally relies on the Revised International Staging System (R-ISS), which incorporates serum beta-2 microglobulin, albumin, lactate dehydrogenase (LDH), and high-risk cytogenetics. This framework helps stratify patients by risk and guides treatment planning. Prognosis varies widely depending on cytogenetic features, response to therapy, and comorbidities. While some patients experience indolent disease for years, others may face aggressive progression with multi-organ involvement.

Evolving Treatment Landscape

The management of multiple myeloma has advanced rapidly with the development of novel agents. First-line treatment often includes triplet regimens combining immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and corticosteroids. Eligible patients may undergo autologous stem cell transplantation (ASCT) after induction therapy. Maintenance therapy, often with lenalidomide, is used to prolong remission. In relapsed or refractory settings, monoclonal antibodies (e.g., daratumumab), next-generation PIs, and selective inhibitors (e.g., selinexor, venetoclax) are deployed. CAR T-cell therapy and bispecific T-cell engagers (BiTEs) represent promising options for heavily pretreated patients.

Supportive Care and Symptom Management

Because multiple myeloma affects multiple organ systems, supportive care is essential. This includes bone-modifying agents such as bisphosphonates or denosumab to reduce skeletal-related events, infection prophylaxis, and management of anemia or renal dysfunction. Pain management, physical therapy, and psychosocial support are critical to preserving function and quality of life. Close monitoring for treatment-related toxicities, including peripheral neuropathy and thromboembolic events, is a key component of comprehensive care.

Research and Emerging Therapies

Ongoing research is focused on identifying new therapeutic targets, refining minimal residual disease (MRD) detection, and optimizing sequencing of therapies. Advances in genomics and proteomics are uncovering novel biomarkers for risk stratification and treatment response. Clinical trials continue to explore the role of cellular therapies, immune checkpoint inhibitors, and combination regimens that enhance depth and durability of response. Personalized medicine approaches are gaining traction, particularly for patients with high-risk cytogenetics or relapsed disease.

Looking Ahead

While multiple myeloma remains incurable, many patients now experience long periods of disease control with good quality of life. The future of myeloma care lies in early detection, precision treatment, and integration of novel therapies. As research uncovers new insights into disease biology and resistance mechanisms, the goal is to transform myeloma into a chronic, manageable condition—and eventually, to achieve functional cures. Collaboration among researchers, clinicians, and patient advocates will be essential in continuing this progress and expanding access to innovative care.