Phase I/II trial of GN-BVC, a gemcitabine and vinorelbine-containing conditioning regimen for autologous hematopoietic cell transplantation in recurrent and refractory hodgkin lymphoma.
Autologous hematopoietic cell transplantation with augmented BCNU regimens is effective treatment for recurrent or refractory Hodgkin lymphoma (HL); however, BCNU-related toxicity and disease recurrence remain challenges. We designed a conditioning regimen with gemcitabine in combination with vinorelbine in an effort to reduce the BCNU dose and toxicity without compromising efficacy. In this phase I/II dose escalation study, the gemcitabine maximum tolerated dose (MTD) was determined at 1250 mg/m(2), and a total of 92 patients were treated at this dose to establish safety and efficacy. The primary endpoint was the incidence of BCNU-related toxicity. Secondary endpoints included 2-year freedom from progression (FFP), event-free survival (EFS), and overall survival (OS). Sixty-eight patients (74%) had 1 or more previously defined adverse risk factors for transplant (stage IV at relapse, B symptoms at relapse, greater than minimal disease pretransplant). The incidence of BCNU-related toxicity was 15% (95% confidence interval, 9%-24%). Only 2% of patients had a documented reduction in diffusing capacity of 20% or greater. With a median follow-up of 29 months, the FFP at 2 years was 71% and the OS at 2 years was 83%. Two-year FFP was 96%, 72%, 67%, and 14% for patients with 0 (n = 24), 1 (n = 37), 2 (n = 23), or 3 (n = 8) risk factors, respectively. Regression analysis identified PET status pretransplant and B symptoms at relapse as significant prognostic factors for FFP. This new transplant regimen for HL resulted in decreased BCNU toxicity with encouraging FFP and OS. A prospective, risk-modeled comparison of this new combination with other conditioning regimens is warranted.
Arai
Sally
S
Department of Medicine, Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, California 94305, USA. sarai1@stanford.edu
Letsinger
Renee
R
Wong
Ruby M
RM
Johnston
Laura J
LJ
Laport
Ginna G
GG
Lowsky
Robert
R
Miklos
David B
DB
Shizuru
Judith A
JA
Weng
Wen-Kai
WK
Lavori
Philip W
PW
Blume
Karl G
KG
Negrin
Robert S
RS
Horning
Sandra J
SJ
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006689:Hodgkin Disease / Q000188:drug therapy / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000628:therapy; D011446:Prospective Studies; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014182:Transplantation, Autologous; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077235:Vinorelbine; D055815:Young Adult; D000093542:Gemcitabine
D003841:Deoxycytidine; D014747:Vinblastine; D000077235:Vinorelbine; D002330:Carmustine; D000093542:Gemcitabine