A Phase II trial of autologous stem cell transplantation followed by mini-allogeneic stem cell transplantation for the treatment of multiple myeloma: an analysis of Eastern Cooperative Oncology Group ECOG E4A98 and E1A97.
Conventional allogeneic hematopoietic stem cell transplantation (HSCT) for multiple myeloma is associated with high transplantation-related mortality (TRM). Nonmyeloablative allogeneic transplantation (NST) uses the well-known graft-versus-myeloma (GVM) effect to eradicate minimal residual disease. The Eastern Cooperative Oncology Group conducted a Phase II trial of autologous HSCT followed by NST to provide maximal tumor cytoreduction to allow for a subsequent GVM effect. Patients received melphalan 200 mg/m(2) with autologous HSCT, followed by fludarabine 30 mg/m(2) in 5 daily doses and cyclophosphamide 1 g/m(2) in 2 daily doses with matched sibling donor NST. Graft-versus-host disease (GVHD) prophylaxis included cyclosporine and corticosteroids. The primary endpoints were TRM, graft failure, acute GVHD, progression-free survival (PFS), and overall survival (OS). Thirty-two patients were enrolled into the study; 23 patients completed both transplantations (72%). Best responses post-NST were 7 (30%) complete remission (CR), 11 (48%) partial remission (PR), 2 (9%) no response, and 3 (13%) not evaluable. Acute grade III-IV GVHD was observed in 4 patients (17%), and chronic GVHD was seen in 13 patients (57%; 7 limited, 6 extensive). Chronic GVHD resulted in the following responses: 3 (23%) CR, 1 continuing CR, and 6 (46%) PR. Two patients (8.7%) had early TRM. With a median follow up of 4.6 years, the median PFS was 3.6 years, and the 2-year OS was 78%. Our findings indicate that autologous HSCT followed by NST is feasible, with a low early TRM in a cooperative group setting. The overall response rate was 78%, including 30% CR, similar to other reports for autologous HSCT-NST. Because a plateau in PFS or OS was not observed with this treatment approach even in patients achieving CR, we suggest that future studies use posttransplantation maintenance therapy.
Vesole
David H
DH
Department of Medicine, St Vincent's Comprehensive Cancer Center, New York, New York, USA. dvesole@lumc.edu
Zhang
Lijun
L
Flomenberg
Neal
N
Greipp
Philip R
PR
Lazarus
Hillard M
HM
Huff
Carol A
CA
D000328:Adult; D000368:Aged; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D020350:Graft vs Tumor Effect; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000401:mortality / Q000628:therapy*; D011292:Premedication; D012086:Reoperation; D016019:Survival Analysis; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan