High-dose chemo-radioimmunotherapy with autologous stem cell support for relapsed mantle cell lymphoma.
Relapsed mantle cell lymphoma is a radiation-sensitive malignancy that is unlikely to be cured by treatment with conventional high-dose therapy and autologous stem cell transplantation. We tested the safety and efficacy of using a CD20-specific monoclonal antibody conjugated with (131)I to deliver high-dose radiation selectively to all lymphoma sites. Patients with relapsed or refractory mantle cell lymphoma received infusions of (131)I-labeled CD20-specific monoclonal antibody (Tositumomab). The antibody dose was 1.7 mg/kg body weight, and the amount of (131)I was calibrated to deliver 20 to 25 Gy to vital normal organs. This treatment was followed 10 days later by administration of high-dose etoposide (30-60 mg/kg), cyclophosphamide (60-100 mg/kg), and infusion of cryopreserved autologous stem cells. The 16 patients in this study had received a median of 3 prior treatments, and 7 had chemotherapy-resistant disease. The median dose of (131)I was 510 mCi (18.87 GBq). There were no therapy-related deaths. Among the 11 patients with conventionally measurable disease at the time of treatment, the respective complete and overall response rates were 91% and 100%. Fifteen patients remain alive, and 12 have had no progression of lymphoma at 6 to 57 months from transplantation and 16 to 97 months from diagnosis. Overall survival at 3 years from transplantation is estimated at 93%, and progression-free survival is estimated at 61%. High-dose treatment with (131)I-Tositumomab, etoposide, and cyclophosphamide results in a high remission rate and may provide long-term disease-free survival for patients with relapsed or refractory mantle cell lymphoma.
Gopal
Ajay K
AK
Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA. agopal@u.washington.edu
Rajendran
Joseph G
JG
Petersdorf
Stephen H
SH
Maloney
David G
DG
Eary
Janet F
JF
Wood
Brent L
BL
Gooley
Theodore A
TA
Bush
Sharon A
SA
Durack
Lawrence D
LD
Martin
Paul J
PJ
Matthews
Dana C
DC
Appelbaum
Frederick R
FR
Bernstein
Irwin D
ID
Press
Oliver W
OW
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity; D003131:Combined Modality Therapy / Q000379:methods; D018572:Disease-Free Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D020522:Lymphoma, Mantle-Cell / Q000401:mortality / Q000532:radiotherapy* / Q000628:therapy; D008875:Middle Aged; D016499:Radioimmunotherapy / Q000379:methods*; D012074:Remission Induction; D016879:Salvage Therapy; D015996:Survival Rate; D014182:Transplantation, Autologous
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; C119496:tositumomab I-131