A phase 1/2 trial of high-dose yttrium-90-ibritumomab tiuxetan in combination with high-dose etoposide and cyclophosphamide followed by autologous stem cell transplantation in patients with poor-risk or relapsed non-Hodgkin lymphoma.
We conducted a phase 1/2 trial of high-dose 90Y-ibritumomab tiuxetan in combination with high-dose etoposide (VP-16) 40 to 60 mg/kg (day -4) and cyclophosphamide 100 mg/kg (day -2) followed by autologous stem cell transplantation (ASCT) in 31 patients with CD20+ non-Hodgkin lymphoma (NHL). Patients underwent dosimetry (day -21) with 5 mCi (185 MBq) 111In-ibritumomab tiuxetan following 250 mg/m2 rituximab, followed a week later by 90Y-ibritumomab tiuxetan to deliver a target dose of 1000 cGy to highest normal organ. Bone marrow biopsy was done on day -7 to estimate radiation dose and stem cells were reinfused when the radiation dose was estimated to be less than 5 cGy. The median 90Y-ibritumomab tiuxetan dose was 71.6 mCi (2649.2 MBq; range, 36.6-105 mCi; range, 1354.2-3885 MBq). Histology included follicular lymphoma (n = 12), diffuse large B-cell (n = 14), and mantle cell (n = 5). The median number of prior chemo-therapy treatments was 2. The treatment was well tolerated. The median times to reach an absolute neutrophil count greater than 500/microL and platelet count more than 20,000/microL were 10 days and 12 days, respectively. There were 2 deaths and 5 relapses. At a median follow-up of 22 months, the 2-year estimated overall survival and relapse-free survival rates are 92% and 78%, respectively. We conclude that high-dose 90Y-ibritumomab tiuxetan can be combined safely with high-dose etoposide and cyclophosphamide without an increase in transplant-related toxicity or delayed engraftment.
Nademanee
Auayporn
A
Division of Hematology and Hemapoietic Cell Transplantation, City of Hope National Medical Center, 1500 E Duarte Rd, Duarte, CA 91010, USA. anademanee@coh.org
Forman
Stephen
S
Molina
Arturo
A
Fung
Henry
H
Smith
David
D
Dagis
Andy
A
Kwok
Cheuk
C
Yamauchi
Dave
D
Anderson
Anne-Line
AL
Falk
Peter
P
Krishnan
Amrita
A
Kirschbaum
Mark
M
Kogut
Neil
N
Nakamura
Ryotaro
R
O'donnell
Margaret
M
Parker
Pablo
P
Popplewell
Leslie
L
Pullarkat
Vinod
V
Rodriguez
Roberto
R
Sahebi
Firoozeh
F
Smith
Eileen
E
Snyder
David
D
Stein
Anthony
A
Spielberger
Ricardo
R
Zain
Jasmine
J
White
Christine
C
Raubitschek
Andrew
A
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis* / Q000276:immunology / Q000601:surgery / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011379:Prognosis; D016499:Radioimmunotherapy; D012008:Recurrence; D033581:Stem Cell Transplantation; D015996:Survival Rate; D014182:Transplantation, Autologous; D015021:Yttrium Radioisotopes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D015021:Yttrium Radioisotopes; C422802:ibritumomab tiuxetan; D005047:Etoposide; D003520:Cyclophosphamide