Disease Overview
Multiple myeloma (MM) is a malignant neoplasm of plasma cells that accumulate in the bone marrow, leading to bone destruction and marrow failure. The disease is most frequently diagnosed in individuals aged 65–74 years. The American Cancer Society estimates 35,730 new cases and 12,590 deaths in the United States in 2023.
Management Recommendations
- Monitoring Strategies
- Asymptomatic (Smoldering) MM:
- Monitor with 24-hour urine total protein, urine protein electrophoresis (UPEP), and urine immunofixation electrophoresis (UIFE) if baseline abnormalities or significant changes in free light chain (FLC) levels occur.
- Symptomatic MM:
- Laboratory tests for toxicity monitoring should include complete blood count (CBC) with differential and comprehensive metabolic panel (CMP) (platelet count, blood glucose, and electrolytes removed in this update).
- Asymptomatic (Smoldering) MM:
- Hematopoietic Stem Cell Transplantation (HSCT)
- For transplant-eligible patients:
- Collect autologous peripheral blood stem cells (PBSCs) within the first 6 cycles of therapy (before prolonged exposure to lenalidomide and/or daratumumab).
- If delayed HSCT is planned, cryopreserve autologous stem cells for future use.
- For transplant-eligible patients:
Treatment of Relapsed/Refractory MM
- Preferred Regimens
- For patients with 1–3 prior lines of therapy and sensitivity to bortezomib and/or lenalidomide:
- Carfilzomib + dexamethasone + daratumumab (Category 1): Demonstrated deeper responses and improved progression-free survival (PFS) in trials.
- Isatuximab + elotuzumab/carfilzomib + dexamethasone (Category 1): Superior median PFS compared to carfilzomib/dexamethasone alone.
- For patients with 1–3 prior lines of therapy and sensitivity to bortezomib and/or lenalidomide:
- Other Regimens
- Carfilzomib + pomalidomide + dexamethasone:
- Achieved very good partial response (VGPR) in 75% and complete response (CR) in 37% of patients in studies.
- Daratumumab + pomalidomide + dexamethasone:
- For patients with ≥1 prior line (including immunomodulatory agents and proteasome inhibitors), this regimen shows promising overall response rates (ORR) and PFS.
- Carfilzomib + pomalidomide + dexamethasone:
Guideline Application
The 2024.V4 NCCN guidelines provide detailed recommendations for standardized diagnosis and treatment of MM. However, clinicians must tailor therapy based on patient-specific factors, including age, comorbidities, and disease biology. As medical research evolves, these guidelines will continue to incorporate new evidence and clinical best practices to optimize patient outcomes.
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