Treatment Options for Relapsed or Refractory Multiple Myeloma

Relapses occur for almost all patients after induction therapy, consolidation with autologous stem cell transplant (SCT), and maintenance therapy. During initial therapy, some patients have poor disease response, or their disease progresses. The general strategy is to give new therapies sequentially as required. In fit patients, reinduction therapy with response may be consolidated with an autologous SCT or allogeneic SCT in some cases. Sometimes, when relapse occurs 1 year or more after initial therapy, the same drugs can be administered a second time.

A subgroup of patients who do not achieve a response to induction chemotherapy have stable disease and a survival prognosis that is as good as that for responding patients.[1,2] When the stable nature of the disease becomes established, these patients can discontinue therapy until the myeloma begins to progress again. Other patients with primary refractory myeloma and progressive disease require a change in therapy. For more information, see the Treatment of Multiple Myeloma section.

For patients with disease response to initial therapy, the myeloma growth rate, as measured by the monoclonal (or myeloma) protein-doubling time, increases progressively with each subsequent relapse, and remission durations become shorter and shorter. Marrow function becomes increasingly compromised as patients develop pancytopenia and enter a refractory phase; occasionally, the myeloma cells dedifferentiate and extramedullary plasmacytomas develop. The myeloma cells may still be sensitive to chemotherapy, but the regrowth rate during relapse is so rapid that progressive improvement is not observed.

Combinations of drugs or single agents may be given sequentially as required. The goal is to avoid symptoms and adverse consequences of relapsing disease. However, the onset of therapy may be delayed because of slow disease progression and good performance status.

Treatment options for relapsed or refractory multiple myeloma include: