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    Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment for Multiple Myeloma

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    Tandem autologous bone marrow or peripheral stem cell transplantation

    Another approach to high-dose therapy has been the use of two sequential episodes of high-dose therapy with stem cell support (tandem transplants).[98,99,100,101,102]

    Evidence (tandem autologous bone marrow or peripheral stem cell transplantation):

    1. A meta-analysis of six randomized clinical trials enrolling 1,803 patients compared single autologous hematopoietic cell transplantation with tandem autologous hematopoietic cell transplantation.
      • There was no difference in OS (HR, 0.94; 95% CI, 0.77-1.14) or in EFS (HR, 0.86; 95% CI, 0.70-1.05).[103][Level of evidence: 1A]
    2. In a trial of 194 previously untreated patients aged 50 to 70 years, the patients were randomly assigned to either conventional oral melphalan and prednisone or VAD for two cycles followed by two sequential episodes of high-dose therapy (melphalan 100 mg/m2) with stem cell support.[88]
      • With a median follow-up of more than 3 years, the double transplant group had superior EFS (37% vs. 16% at 3 years, P < .001) and OS (77% vs. 62%, P < .001).[88][Level of evidence: 1iiA]
    3. Five different groups have compared two tandem autologous transplants with one autologous transplant followed by a reduced-intensity conditioning allograft from an HLA-identical sibling; treatment assignment was based on the presence or absence of an HLA-identical sibling. The results have been discordant for survival in these nonrandomized trials.
      • One study showed a survival advantage for the two tandem autologous transplants.[104][Level of evidence: 3iiiA]
      • Two studies showed a survival advantage for the autologous transplant followed by an allogeneic transplant.[105,106][Level of evidence: 3iiiA]
      • Two studies showed no difference in OS.[107,108][Level of evidence: 3iiiA]
    4. A trial of 195 patients younger than 60 years with newly diagnosed myeloma randomly compared two tandem transplants with a single autologous stem cell transplant followed by 6 months of maintenance therapy with thalidomide.
      • With a median follow-up of 33 months, the thalidomide maintenance arm showed a benefit in PFS (85% vs. 57% at 3 years, P = .02) and OS (85% vs. 65% at 3 years, P = .04).[109][Level of evidence: 1iiA]
    5. Six clinical trials compared the outcomes of patients receiving tandem autologous transplant to those of patients receiving a reduced-intensity allogeneic SCT after autologous transplant. Patients were assigned to the latter treatments based on the availability of an HLA-matched donor. Two meta-analyses of these data showed that although the complete remission rate was higher in patients undergoing reduced-intensity allogeneic SCT, OS was comparable because of an increased incidence of nonrelapse mortality with allogeneic transplant.[110,111][Level of evidence: 1iiA]
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