Treatment for Multiple Myeloma
Interferon maintenance after stem cell transplantation
- In a randomized study of 84 patients following autologous bone marrow transplantation, maintenance therapy with interferon showed a benefit in PFS (46 mo vs. 27 mo, P < .025) and OS (75% vs. 50%, P < .01).[Level of evidence: 1iiA]
- A larger randomized trial of 805 patients showed no difference in PFS or OS with interferon given after peripheral stem cell transplantation or conventional chemotherapy.[Level of evidence: 1iiA]
High-dose chemotherapy: Allogeneic bone marrow or peripheral stem cell transplantation
In a registry of 162 patients who underwent allogeneic matched sibling-donor transplants, the actuarial OS rate was 28% at 7 years.[Level of evidence: 3iiiA]
Favorable prognostic features included the following:
- Low tumor burden.
- Responsive disease before transplant.
- Application of transplantation after first-line therapy.
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.[90,91,92,93]
Allogeneic marrow transplants have significant toxic effects (15%-40% mortality), but the possibility of a potent and possibly curative graft-versus-myeloma effect makes this procedure attractive.[93,94]
Further research is required to make allogeneic transplants less dangerous and to find methods for initiating an autoimmune response to the myeloma cells. Nonmyeloablative allogeneic stem cell transplant is under development.[95,96,97] Such strategies aim to maintain efficacy (so called graft-versus-tumor effect) while reducing transplant-related mortality.[98,99]
Myeloma patients who respond to treatment show a progressive fall in the M protein until a plateau is reached; subsequent treatment with conventional doses does not result in any further improvement. This has led investigators to question how long treatment should be continued.
- In a single study, it was observed that maintenance therapy with MP prolonged the initial remission duration (31 mo) compared with no maintenance treatment (23 mo).
- No effect on OS was found because the majority of patients who relapsed in the no maintenance arm responded again to MP, while those on maintenance MP did not respond to further treatment.
- The Canadian group  suggests that induction chemotherapy be continued as long as the M protein continues to fall; therapy can be discontinued after the M protein reaches a plateau that remains stable for 4 months.
- Maintenance interferon-alpha therapy has been reported in several studies to prolong initial remission duration.[101,102,103,104] While the impact of interferon maintenance on disease-free survival and OS has significantly varied among trials, a meta-analysis of 1,543 patients treated on 12 trials randomizing between interferon maintenance and observation indicated that interferon maintenance was associated with improved relapse-free survival (27% vs. 19% at 3 years, P < .001) and OS (12% odds reduction, P = .04). Toxic effects in this population may be substantial and must be balanced against the potential benefits in response duration.
- Maintenance therapy with interferon showed a benefit in PFS (46 mo vs. 27 mo, P < .025) and OS (75% vs. 50%, P < .01) in a randomized study of 84 patients following autologous bone marrow transplantation.[Level of evidence: 1iiA] A larger randomized trial of 805 patients showed no difference in PFS or OS with interferon given after peripheral stem cell transplantation or conventional chemotherapy.[Level of evidence: 1iiA]
- A study of 125 responding patients with first-line VAD induction who were randomly assigned to maintenance corticosteroids at 10 mg or 50 mg on alternate days showed improved PFS (14 mo vs. 5 mo, P = .003) and OS (36 mo vs. 26 mo, P = .05) for the patients receiving the higher-dose corticosteroids.[Level of evidence: 1iiA]
- In a larger trial by the National Cancer Institute of Canada (CAN-NCIC-MY7) of 585 patients treated with first-line MP, 292 patients were randomly assigned to pulse dexamethasone (40 mg a day for 4 days monthly) versus no maintenance.
- PFS favored the dexamethasone maintenance arm (2.8 y vs. 2.1 y, P = .002), but there was no difference in OS (4.1 y vs. 3.8 y, P = .4).[Level of evidence: 1iiDiii]
- Two months after autologous transplantation, 597 patients younger than 65 years were randomly assigned to no maintenance, pamidronate, or pamidronate plus thalidomide.
- The thalidomide arm was favored by EFS (36% vs. 37% vs. 52%, P < .009) and by OS at 4 years (77% vs. 74% vs. 87%, P < .04), while no differences were seen for skeletal events.[Level of evidence: 1iiA]
- After autologous transplantation, 129 patients were randomly assigned to indefinite prednisone versus indefinite prednisone with 12 months of thalidomide.
- With a median follow-up of 3 years, the thalidomide arm was favored by PFS (42% vs. 23%, P < .001) and by OS at 3 years (86% vs. 75%, P = .004).[Level of evidence: 1iiA]