Multiple Myeloma

Multiple myeloma is a malignancy of plasma cells in the bone marrow. These abnormal cells produce monoclonal immunoglobulins (M protein) that damage bones, kidneys, and immune function. Myeloma often evolves from monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma, making early surveillance vital.

Risk Factors

• Age > 60, male sex
• African ancestry
• Family history of MGUS/myeloma
• Obesity, radiation, certain pesticides
• Chronic antigenic stimulation or autoimmune disease

Symptoms & CRAB Criteria

• Calcium elevation (hypercalcemia): thirst, confusion, constipation
• Renal impairment: elevated creatinine, proteinuria
• Anemia: fatigue, pallor
• Bone lesions: pain, fractures, lytic lesions on imaging
• Recurrent infections, weight loss, neuropathy (amyloidosis)

Diagnosis

• Serum protein electrophoresis (SPEP), immunofixation, free light chains
• 24-hour urine protein electrophoresis
• Bone marrow biopsy showing ≥10% clonal plasma cells
• Advanced imaging: low-dose whole-body CT, PET-CT, or MRI for bone lesions
• Staging (Revised ISS) uses β2-microglobulin, albumin, LDH, cytogenetics

Smoldering vs Active

• Smoldering Myeloma: M protein ≥ 3 g/dL and/or plasma cells 10–60% without CRAB signs.
• Active Myeloma: CRAB features or myeloma-defining events (≥60% plasma cells, kappa/lambda ratio ≥100, >1 MRI focal lesion).
• High-risk smoldering patients may be treated to delay progression.

Treatment Approach

Initial Therapy (fit patients)

• Triplet or quadruplet regimens (daratumumab + VRd; KRd)
• Autologous stem cell transplant (ASCT) for eligible individuals
• Maintenance therapy (lenalidomide, +/- proteasome inhibitor) post-ASCT

For Transplant-Ineligible

• Doublet or triplet regimens (e.g., DRd, VRd-lite) tailored to comorbidities

Relapsed/Refractory

• Immunomodulators (lenalidomide, pomalidomide)
• Proteasome inhibitors (bortezomib, carfilzomib, ixazomib)
• Monoclonal antibodies (daratumumab, isatuximab, belantamab)
• Selinexor, venetoclax (t(11;14) patients), CAR-T, bispecific antibodies

Supportive Care

• Bisphosphonates or denosumab for bone protection
• Vaccinations, antivirals (acyclovir), IVIG for infections
• Erythropoietin-stimulating agents for anemia
• Radiation for painful focal lesions

Living with Myeloma

• Track labs (M protein, light chains), kidney function, bone scans
• Monitor for peripheral neuropathy, DVT, and medication side effects
• Maintain exercise and bone-strengthening routines (with caution)
• Prioritize mental health—myeloma is chronic but increasingly treatable

Complications

• Renal failure, hypercalcemia crisis
• Pathologic fractures, spinal cord compression
• Increased infection risk, shingles (consider vaccines)
• Secondary malignancies, treatment-related toxicities

Research & Future Directions

Advances include bispecific T-cell engagers, next-gen CAR-T, targeted degradation of oncogenic drivers, and personalized MRD-guided therapy.

Experimental & Emerging Treatments

• BCMA Bispecific Antibodies (teclistamab, elranatamab): Off-the-shelf immunotherapies redirect T cells to myeloma cells.
• Next-Gen CAR-T (dual-target): Simultaneously target BCMA + GPRC5D/FCRL5 to reduce relapse.
• CELMoDs (iberdomide): Novel cereblon modulators more potent than current IMiDs.
• MRD-Guided Adaptive Therapy: Trials adjust treatment intensity based on minimal residual disease levels to balance efficacy and toxicity.

Track Myeloma with Diagnoza.care

Stay Ahead of Myeloma – Log labs, imaging, treatment cycles, transfusions, side effects, and supportive therapies, schedule oncology visits and infusion center appointments, and let the AI companion highlight trends that require attention.

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Medical Disclaimer: Informational only. Follow your hematologist/oncologist’s plan for diagnostics, therapies, and transplant/CAR-T evaluations. Sources: National Comprehensive Cancer Network, International Myeloma Working Group, American Society of Hematology