|  | Cancer | Cancer Treatment

Multiple Myeloma Management: Current Therapies, Transplant & Supportive Care

Multiple myeloma (MM) is a plasma cell malignancy characterized by clonal proliferation in bone marrow, monoclonal protein production, and end-organ damage (CRAB: hyperCalcemia, Renal insufficiency, Anemia, Bone lesions). While incurable, outcomes have dramatically improved with triplet/quadruplet regimens and autologous stem cell transplant (ASCT).

Initial Workup & Risk Stratification

  • Diagnostic criteria: ≥10% clonal plasma cells or plasmacytoma + ≥1 myeloma-defining event (CRAB, SLiM: ≥60% plasma cells, serum free light chain ratio ≥100, >1 focal lesion on MRI)
  • Staging: R-ISS (Revised International Staging System): ISS stage + high-risk cytogenetics (del17p, t(4;14), t(14;16)) + elevated LDH
  • Standard-risk vs. high-risk guides intensity of therapy

Frontline Therapy (Transplant-Eligible)

  1. Induction (4–6 cycles): Quadruplet preferred: Dara-VRd (daratumumab + bortezomib + lenalidomide + dexamethasone) per PERSEUS/GRIFFIN trials. Triplet VRd alternative.
  2. Stem cell mobilization: G-CSF ± plerixafor
  3. High-dose melphalan (200 mg/m²) + ASCT: Consolidation standard; tandem transplant not routinely recommended
  4. Maintenance: Lenalidomide indefinitely until progression/toxicity (CALGB 100104, IFM 2005-02)

Frontline Therapy (Transplant-Ineligible)

  • Dara-Rd (daratumumab + lenalidomide + dexamethasone) — MAIA trial standard
  • VRd-lite (dose-reduced VRd) or Rd if frail
  • Continuous therapy until progression

Relapsed/Refractory MM: Sequencing Principles

  • Switch drug classes at each relapse (proteasome inhibitor → IMiD → anti-CD38 → BCL2 inhibitor → T-cell redirectors)
  • Key agents: Carfilzomib, pomalidomide, isatuximab, selinexor, belantamab mafodotin (withdrawn US), ide-cel/cilta-cel (BCMA CAR-T), teclistamab/elranatamab (bispecifics)
  • Clinical trials encouraged at every relapse

Supportive Care Essentials

ComplicationManagement
Bone diseaseZoledronic acid or denosumab q4–12w; calcium/vit D; weight-bearing exercise
Infection prophylaxisIVIG if IgG <400 mg/dL + recurrent infections; antimicrobial prophylaxis (TMP-SMX, acyclovir) during high-dose steroids/transplant
Renal protectionHydration, avoid NSAIDs/contrast, bortezomib-based regimens (non-renal clearance)
NeuropathyBortezomib SC (not IV); dose-reduce; gabapentinoids, duloxetine
VTE prophylaxisAspirin (low risk) or LMWH/DOAC (high risk: IMID + steroids + immobility)

Monitoring Response (IMWG Criteria)

  • sCR (stringent CR), CR, VGPR, PR, SD, PD — based on M-protein, FLC, bone marrow, imaging
  • MRD (minimal residual disease) by NGS/flow (10⁻⁵–10⁻⁶) increasingly guides maintenance duration

MM management is rapidly evolving. Treatment at a myeloma center with clinical trial access optimizes outcomes.

Cancer Treatment - Related Articles