Background
In this trial of the treatment of newly diagnosed multiple myeloma, we compared a
protocol that entailed a hematopoietic stem-cell autograft followed by an allograft
from an HLA-identical sibling with a protocol of tandem autografts.
Methods
We enrolled 162 consecutive patients with newly diagnosed myeloma who were 65
years of age or younger and who had at least one sibling. All patients were initially
treated with vincristine, doxorubicin, and dexamethasone, followed by melphalan
and autologous stem-cell rescue. Patients with an HLA-identical sibling then received
nonmyeloablative total-body irradiation and stem cells from the sibling. Patients
without an HLA-identical sibling received two consecutive myeloablative doses of
melphalan, each of which was followed by autologous stem-cell rescue. The primary
end points were overall survival and event-free survival.
Results
After a median follow-up of 45 months (range, 21 to 90), the median overall survival
and event-free survival were longer in the 80 patients with HLA-identical siblings
than in the 82 patients without HLA-identical siblings (80 months vs. 54 months,
P = 0.01; and 35 months vs. 29 months, P = 0.02, respectively). Among patients who
completed their assigned treatment protocols, treatment-related mortality did not
differ significantly between the double-autologous-transplant group (46 patients)
and the autograft–allograft group (58 patients, P = 0.09), but disease-related mortality
was significantly higher in the double-autologous-transplant group (43% vs. 7%,
P<0.001). The cumulative incidence rates of grades II, III, and IV graft-versus-host
disease (GVHD) combined and of grade IV GVHD in the autograft–allograft group
were 43% and 4%, respectively. Overall, 21 of 58 patients (36%) were in complete
remission after a median follow-up of 38 months (range, 10 to 72) after allografting.
Of the 46 patients who received two autografts, 25 (54%) died.
Conclusions
Among patients with newly diagnosed myeloma, survival in recipients of a hematopoietic
stem-cell autograft followed by a stem-cell allograft from an HLA-identical
sibling is superior to that in recipients of tandem stem-cell autografts. (ClinicalTrials.
gov number, NCT00415987.)
