Phase I trial of iodine-131 tositumomab with high-dose chemotherapy and autologous stem-cell transplantation for relapsed non-Hodgkin's lymphoma.
OBJECTIVE
To determine the maximum outpatient dose of iodine-131 tositumomab (up to 0.75 Gy) combined with high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) followed by autologous stem-cell transplantation (ASCT) for the treatment of chemotherapy-resistant relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL).


METHODS
Twenty-three patients with chemotherapy-refractory or multiply-relapsed B-cell NHL were treated in a phase I trial combining iodine-131 tositumomab (ranging from 0.30 to 0.75 Gy total-body dose [TBD]) with high-dose BEAM followed by ASCT.


RESULTS
The complete response rate after transplantation was 57%, and the overall response rate was 65%. Short-term and long-term toxicities were similar to historical control patients treated with BEAM alone. With a median follow-up of 38 months (range, 27 to 60 months), the overall survival (OS) rate was 55%, and the event-free survival (EFS) rate was 39%.


CONCLUSIONS
There were no significant added toxicities apparent with the addition of iodine-131 tositumomab up to a dose of 0.75 Gy TBD to high-dose BEAM chemotherapy followed by ASCT. The EFS and OS were encouraging in this group of chemotherapy-resistant or refractory B-cell NHL patients. A follow-up phase II trial with iodine-131 tositumomab at the dose of 0.75 Gy TBD with BEAM is currently ongoing.
Vose
Julie M
JM
Section of Hematology/Oncology, University of Nebraska Medical Center, 987680 Nebraska Medical Center, Omaha, NE 68198-7680, USA. jmvose@unmc.edu
Bierman
Philip J
PJ
Enke
Charles
C
Hankins
Jordan
J
Bociek
Gregory
G
Lynch
James C
JC
Armitage
James O
JO
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects*; D018951:Antigens, CD20; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002330:Carmustine / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D016499:Radioimmunotherapy; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D003561:Cytarabine; D005047:Etoposide; C119496:tositumomab I-131; D008558:Melphalan; D002330:Carmustine