Plasma Cell Neoplasms: Multiple Myeloma, MGUS, and Plasmacytoma — Overview, Diagnosis & Treatment Options | MyMedicPlus

Plasma cell neoplasms encompass multiple myeloma (MM), smoldering myeloma, monoclonal gammopathy of undetermined significance (MGUS), and solitary plasmacytoma. Multiple myeloma is the most common, representing approximately 10% of hematologic malignancies with approximately 35,000 new cases per year in the US.

MGUS is the universal precursor to MM (1% annual progression rate). Risk factors include African American ethnicity (2x risk), age over 65, male sex, obesity, and agricultural chemical exposure. High-risk chromosomal abnormalities — del(17p), t(4;14), t(14;16), gain(1q) — predict aggressive disease requiring intensified treatment.

CRAB criteria define symptomatic myeloma requiring treatment: hyperCalcemia, Renal insufficiency, Anemia (normocytic), Bone lesions (lytic lesions, pathological fractures, osteoporosis). Additional features: fatigue, recurrent bacterial infections (hypogammaglobulinemia), peripheral neuropathy (AL amyloidosis), and hyperviscosity syndrome.

Serum protein electrophoresis (SPEP) with immunofixation, serum free light chains (kappa/lambda), and 24-hour urine UPEP. Bone marrow biopsy confirms clonal plasma cells (≥10% for MM). Whole-body low-dose CT or PET/CT for lytic bone lesions. FISH cytogenetics for del(17p), t(4;14), t(14;16) — essential for risk stratification. R-ISS staging.

Transplant-eligible: induction with daratumumab-VRd (bortezomib, lenalidomide, dexamethasone) followed by autologous stem cell transplantation (ASCT) plus lenalidomide maintenance. Transplant-ineligible: daratumumab-VRd or VRd. Relapsed: carfilzomib, pomalidomide, venetoclax (t(11;14)). CAR-T cells (idecabtagene vicleucel, ciltacabtagene autoleucel) approved for heavily pre-treated patients. Bispecific antibodies (teclistamab, elranatamab) for refractory disease.

Median OS with modern therapy has improved dramatically to over 7-8 years. Standard-risk myeloma: median OS exceeds 10 years. High-risk myeloma (del17p, t(4;14)): median OS approximately 4 years. MRD (minimal residual disease) negativity after treatment is the strongest predictor of durable remission and extended survival.