Treatment for Multiple Myeloma
Single autologous bone marrow or peripheral stem cell transplantation
While some prospective randomized trials, such as the U.S. Intergroup trial SWOG-9321, have shown improved survival for patients who received autologous peripheral stem cell or bone marrow transplantation after induction chemotherapy versus chemotherapy alone,[66,67,68][Level of evidence: 1iiA] other trials have not shown any survival advantage.[69,70,71,72][Level of evidence: 1iiA]
Two meta-analyses of almost 3,000 patients showed no survival advantage.[73,74][Level of evidence: 1iiA]
Even the trials suggesting improved survival showed no signs of a slowing in the relapse rate or a plateau to suggest that any of these patients had been cured.[66,67,68,75]
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).[76,77,78,79,80]
- 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 event-free survival (EFS) (HR = 0.86; 95% CI, 0.70-1.05).[Level of evidence: 1A]
- 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.
- 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).[Level of evidence: 1iiA]
- Three 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.
- One study showed a survival advantage for the autologous transplant followed by an allogeneic transplant.
- One study showed no difference in OS.[82,83,84,85][Level of evidence: 3iiiA]
- With a median follow-up of 45 months, the median OS was 54 months for the tandem autologous grafts versus 80 months for the allogeneic graft (P = .01).[Level of evidence: 3iiA]
- 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).[Level of evidence: 1iiA]