What Exactly Happens in Multiple Myeloma?

Under normal circumstances, B-lymphocytes in the bone marrow mature into plasma cells, which synthesise immunoglobulins (antibodies) in response to infection. In multiple myeloma, a single abnormal plasma cell undergoes malignant change and proliferates — producing large quantities of a non-functional antibody (the M-protein) while simultaneously suppressing the production of normal antibodies. The accumulating myeloma cells also activate osteoclasts (bone-destroying cells), leading to characteristic bone lesions. The resulting combination of bone destruction, immune suppression, anaemia and kidney damage defines the clinical picture of myeloma.

It is also important to note that not all plasma cell disorders require immediate treatment. Conditions such as MGUS (monoclonal gammopathy of undetermined significance) and smouldering myeloma are monitored closely without treatment until active myeloma criteria are met.

Types and Classification of Plasma Cell Disorders

Multiple myeloma exists on a spectrum of plasma cell disorders, and accurate classification determines whether and when treatment should begin.

MGUS (Monoclonal Gammopathy of Undetermined Significance): A pre-malignant plasma cell condition with less than 10% clonal plasma cells in the bone marrow and no organ damage. Requires monitoring but not treatment. The annual risk of progression to myeloma is approximately 1%.

Smouldering Multiple Myeloma (SMM): An intermediate condition with higher plasma cell burden (10–60%) or higher M-protein levels but still no CRAB criteria or biomarkers of malignancy. Higher risk of progression than MGUS. Managed with active monitoring; select high-risk SMM patients may now be offered early treatment in clinical trial settings.

Active Multiple Myeloma: Meets CRAB criteria or has biomarkers of malignancy (60% or more clonal plasma cells, serum free light chain ratio of 100 or higher, or more than one focal lesion on MRI). Requires treatment.

Light Chain Myeloma: Plasma cells produce only free light chains (kappa or lambda) without intact immunoglobulin. Diagnosed by serum free light chain assay and 24-hour urine electrophoresis. Associated with a higher risk of renal damage.

Non-Secretory Myeloma: Plasma cells produce neither intact immunoglobulin nor detectable free light chains. Diagnosis and monitoring rely on bone marrow biopsy and imaging rather than serum markers.

IgG, IgA, IgM, IgD, IgE Myeloma: Classified by the type of immunoglobulin heavy chain produced. IgG is the most common; IgA is associated with higher rates of hyperviscosity; IgD and IgE myelomas are rare but often present at an advanced stage.

Plasma Cell Leukaemia: A rare, aggressive form of myeloma where clonal plasma cells circulate in the peripheral blood (≥20% or >2×10⁹/L). Requires intensive treatment.

Solitary Plasmacytoma: A localised plasma cell tumour, either in bone (solitary bone plasmacytoma) or soft tissue (extramedullary plasmacytoma), without systemic myeloma criteria. Treated with radiation; many eventually progress to systemic myeloma.

Symptoms of Multiple Myeloma

Multiple myeloma is captured by the acronym CRAB in clinical medicine:

• C — Calcium elevation (hypercalcaemia): caused by bone breakdown, leading to confusion, constipation, nausea and excessive thirst

• R — Renal impairment: M-proteins can clog kidney tubules, leading to kidney failure

• A — Anaemia: bone marrow crowding reduces red blood cell production, causing fatigue and breathlessness

• B — Bone lesions: punched-out lytic lesions on X-ray, bone pain (particularly in the back and ribs) and increased fracture risk

Additional symptoms may include recurrent infections due to impaired immunity, weight loss, and peripheral neuropathy — tingling or numbness in the hands and feet, sometimes worsened by certain treatments.

How Is Multiple Myeloma Diagnosed?

Diagnosis involves blood tests (serum protein electrophoresis — SPEP — detects the M-protein spike; full blood count; creatinine and calcium for organ involvement; beta-2 microglobulin and LDH as prognostic markers); 24-hour urine protein electrophoresis to detect Bence Jones proteins; serum free light chain assay; whole-body low-dose CT or PET-CT scan to detect bone lesions; and bone marrow biopsy with cytogenetics and FISH testing — identifying chromosomal abnormalities such as del(17p), t(4;14) and t(14;16), which indicate higher-risk disease and influence treatment selection.

Treatment Options — Chemotherapy and Targeted Therapy

Modern treatment is built around combinations of three drug classes:

Proteasome inhibitors: Bortezomib (Velcade) and carfilzomib block the proteasome, leading to myeloma cell death.

Immunomodulatory drugs (IMiDs): Thalidomide, lenalidomide, and pomalidomide modulate the immune system and have direct anti-myeloma activity.

Anti-CD38 monoclonal antibodies: Daratumumab targets the CD38 protein expressed on myeloma cells and is now incorporated into first-line treatment regimens.

Corticosteroids: Dexamethasone is a standard component of most myeloma regimens.

Induction therapy — typically a three-drug combination such as bortezomib-lenalidomide-dexamethasone (VRd) or daratumumab-VRd is given for several cycles before considering transplant or maintenance therapy. Multiple myeloma treatment cost in India varies based on drug regimen, treatment duration, and transplant eligibility. Patients with relapsed or refractory myeloma may also be eligible for clinical trials evaluating next-generation agents discussing trial availability with your haematologist is worthwhile.

Is Bone Marrow Transplant Used for Multiple Myeloma?

Yes. Autologous stem cell transplantation (ASCT) — commonly called bone marrow transplant — remains an important consolidation strategy for eligible myeloma patients. In ASCT, the patient's own stem cells are collected, stored, and reinfused after high-dose chemotherapy (most commonly melphalan) to rescue the bone marrow. It is not a cure but can deepen and prolong remission significantly. Transplant eligibility depends on age, organ function, performance status, and disease response to induction therapy. IOCI Noida's Hemato-Oncology department supports haematological malignancy management Following transplant or induction, lenalidomide maintenance is now standard practice for most patients, prolonging progression-free survival per IMWG and NCCN guidelines.