How does stem cell transplantation affect other treatment decisions in patients with multiple myeloma?

Updated: Aug 14, 2019
  • Author: Sara J Grethlein, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

The approval of new drugs continues to change the landscape of myeloma maintenance therapy. In general, the first decision made in the management of patients with myeloma who require systemic therapy is whether stem cell transplantation is part of the strategy. Considerations are as follows:

  • Minimal residual disease testing of the bone marrow is incorporated into the response evaluation to further determine disease burden in patients who achieve complete remission.
  • Alkylator and nitrosourea therapy is usually deferred or reduced in patients who may require autologous stem cell collection, to avoid injury to the stem cells.

  • All transplant-eligible multiple myeloma patients should receive a triplet induction therapy (immunomodulatory agents, proteasome inhibitor and dexamethasone). Bortezomib with lenalidomide and dexamethasone is the most commonly used regimen, [1]  while the combination of carfilzomib (second-generation proteasome inhibitor) with lenalidomide and dexamethasone showed promising data, particularly in high- risk patients. A clinical trial comparing the two regimens is ongoing.
  • Monoclonal antibodies are a new drug class being integrated to the existing anti-myeloma regimens due to the deeper response rate and better progression-free survival (PFS) seen with the combinations. [2, 3, 4]

  • High-dose melphalan followed by autologous stem cell transplant after induction has been associated with superior event-free survival compared with chemotherapy and is considered the preferred approach. [5]

  • Post-transplantation maintenance therapy with low-dose lenalidomide yields improved PFS and overall survival (OS). Adverse effects include infection, thrombosis, and second primary malignancy. [6]  The oral proteasome inhibitor ixazomib showed improved PFS compared with placebo and may be an alternative choice for patients who do not tolerate lenalidomide. [7]

  • Minimal residual disease testing of the bone marrow is incorporated into the response evaluation to further determine disease burden in patients who achieve complete remission. [8]
  • More sensitive skeletal imaging—including whole-body CT scan, MRI, or PET/CT—is incorporated in the diagnosis and response criteria. [9]
  • Frailty score predicts outcome in transplant-ineligible patients with newly diagnosed myeloma and is incorporated into the staging criteria. [10]
  • Continuous treatment with lenalidomide and dexamethasone [11]  or bortezomib (Velcade), melphalan, and prednisone (VMP) [12]  are the most active regimens for transplant-ineligible patients, although addition of the CD38 monoclonal antibody daratumumab to these regimens to drive deeper response is likely to become new standard of care. [2, 3]

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