A Cochrane review of 14 controlled studies found none of the trials helpful for contemporary treatment decisions regarding single versus tandem transplants. None of the trials employed bortezomib or lenalidomide, and the sharp decrease in compliance with a second transplant complicated sample-size calculations for sufficient statistical power.
High-dose chemotherapy: Allogeneic bone marrow or peripheral stem cell transplantation
Evidence (high-dose chemotherapy: allogeneic bone marrow or peripheral stem cell transplantation):
Many patients are not young enough or healthy enough to undergo these intensive approaches. A definite graft-versus-myeloma effect has been demonstrated, including regression of myeloma relapses following the infusion of donor lymphocytes.
Favorable prognostic features included the following:
- Low tumor burden.
- Responsive disease before transplant.
- Application of transplantation after first-line therapy.
Myeloablative allogeneic stem cell transplantation has significant toxic effects (15%–40% mortality), but the possibility of a potent and possibly curative graft-versus-myeloma effect in a minority of patients may offset the high transplant-related mortality.[113,114,115]
The lower transplant-related mortality from nonmyeloablative approaches has been accompanied by a greater risk of relapse. Since the introduction of lenalidomide and bortezomib, a trial exploring donor versus no donor comparison of autologous stem cell transplantation (SCT) versus autologous SCT and nonmyeloablative allogeneic (SCT) in 260 untreated patients showed no difference in PFS or OS.[Level of evidence: 3iiiA] This result contrasted with two older trials (before introduction of lenalidomide and bortezomib), which suggested improvement of PFS and OS with a sibling donor.[106,117][Level of evidence: 3iiiA] Given the lack of evidence so far that the high-risk patients benefit from allogeneic stem cell transplantation in this era of novel new agents, it remains debatable whether allogeneic stem cell transplantation should be offered in the first-line setting outside the context of a clinical trial.[115,118]
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]