ORLANDO – Allogeneic stem cell transplantation failed to boost overall survival or progression-free survival rates at 3 years when added to autologous stem cell transplantation and compared with tandem autologous transplants among patients with standard-risk myeloma.
Disappointing at best, the experimental strategy dubbed "auto-allo" by investigators also increased treatment-related mortality in this first report from a much-anticipated phase III trial that enrolled 710 patients at 43 centers in the United States.
Dr. Amrita Krishnan
Yet researchers are holding out hope that with longer follow-up, auto-allo might begin to pay off for patients with standard or high-risk disease. Tandem "auto-auto" transplants are known to improve survival, but they are not curative, explained lead author Dr. Amrita Krishnan, director of the multiple myeloma program at the City of Hope cancer center in Duarte, Calif.
"Ultimately, [auto-allo] may lead to a cure for these patients," she said, when pressed to explain the continued interest in the approach. Dr. Krishnan’s presentation at the annual meeting of the American Society of Hematology generated extensive discussion. If there was any audience agreement, it was that for now, use of auto-allo transplants should be confined to clinical trials.
"This is a preliminary result but it certainly is not supportive of routine use of nonmyeloablative allogeneic transplant in the standard-risk patients. ... With longer-term follow-up, if these results hold out, then I think our enthusiasm will [disappear]," said session moderator Dr. Edward A. Stadtmauer, a coinvestigator, professor of medicine, and codirector of the bone marrow and stem cell transplant programs at the University of Pennsylvania in Philadelphia.
The Blood and Marrow Transplant Clinical Trials Network enrolled multiple myeloma patients from December 2003 to March 2007, and assigned them to trial arms based on whether they had an HLA-matched sibling donor at the time of enrollment. All patients received high-dose melphalan 200 mg/m2 and an autologous stem cell transplant. This was followed by a second autologous transplant with melphalan in 484 patients without a sibling match. The 226 patients who had a match received a nonmyeloablative conditioning regimen followed by allogeneic transplant and 2 Gy of total body irradiation. In each group, 82% went on to a second transplant.
Progression-free survival rates at 3 years were 46% in the auto-auto arm and 43% in the auto-allo arm (47% and 44%, respectively, when only patients who received second transplants were analyzed). Overall survival rates, likewise, were similar at 80% and 77%, respectively, as were progression/relapse rates of 46% with auto-auto and 43% with auto-allo.
Only treatment-related mortality was significantly different, at 4% with auto-auto and 12% with auto-allo (P less than .001), a split that Dr. Krishnan attributed to graft-vs.-host effect and graft failure in the allo-allo arm. Myeloma accounted for 70% of deaths in the auto-auto group vs. 38% in the experimental group, she noted.
Patients in the auto-allo group also received maintenance therapy with thalidomide and dexamethasone, but the regimen proved intolerable for 84% of those assigned to it.
The National Heart, Lung, and Blood Institute and the National Cancer Institute fund the Blood and Marrow Transplant Clinical Trials Network. Dr. Krishnan and Dr. Stadtmauer disclosed being on the Celgene speakers bureau.