A phase I study of 90Y-2IT-BAD-Lym-1 in patients with non-Hodgkin's lymphoma.
BACKGROUND
Prior clinical trials proved that all histologic grades of chemotherapy-resistant B-cell non-Hodgkin's lymphoma (NHL) could respond to radio-immunotherapy (RIT) with 131I-Lym-1 and 67Cu-2IT-BAT-Lym-1. This Phase I study was conducted to determine the safety and maximum tolerated dose (MTD) of 90Y-2IT-BAD-Lym-1.


METHODS
Lym-1 is a mouse monoclonal antibody that preferentially targets malignant B-lymphocytes. 90Y has beta emissions suitable for therapy but no gamma emissions, therefore, 111In-2IT-BAD-Lym-1 is used for imaging. The macrocyclic chelator, DOTA, bound 90Y tightly to form a stable drug. Patients with chemotherapy-resistant NHL received 90Y-2IT-BAD-Lym-1 at administered doses of: 0.185, 0.278, or 0.370 GBq/m2.


RESULTS
Myelotoxicity, especially thrombocytopenia, was dose-limiting. No significant non-hematologic toxicity occurred. Human anti-mouse antibody (HAMA) developed in 3/8 patients. The mean radiation dose to the 33 imaged tumors was 7.0 Gy/GBq. Lung, kidney and liver received mean radiation doses of 1.3, 2.4, and 6.4 Gy/GBq, respectively from 90Y-2IT-BAD-Lym-1. The tumor: body and tumor:bone marrow (by imaging) ratios were 16.4:1 and 5.8:1, respectively. In this Phase I study, 5/8 patients that failed prior chemotherapy had a partial response or stabilization of NHL after RIT.


CONCLUSIONS
The safety and toxicity of 90Y-2IT-BAD-Lym-1 were determined and the MTD was 0.370 GBq/m2, a dose used in 4 patients. 90Y-2IT-BAD-Lym-1 may be useful for future clinical trials because 90Y is readily available and can deliver potent beta emissions to NHL. Bone marrow support however, will be required for further dose escalation.
O'Donnell
R T
RT
Department of Internal Medicine, Division of Hematology and Oncology, University of California, Davis Medical Center, Sacramento, California 95816, USA. rtodonnell@ucdavis.edu
Shen
S
S
Denardo
S J
SJ
Wun
T
T
Kukis
D L
DL
Goldstein
D S
DS
Denardo
G L
GL
D000328:Adult; D000368:Aged; D000818:Animals; D000910:Antibodies, Heterophile / Q000097:blood; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D008875:Middle Aged; D018579:Patient Selection; D016499:Radioimmunotherapy / Q000009:adverse effects*; D011877:Radionuclide Imaging; D011879:Radiotherapy Dosage; D012449:Safety; D013921:Thrombocytopenia / Q000209:etiology; D015021:Yttrium Radioisotopes / Q000009:adverse effects*
C410508:2IT-BAD-Lym-1 monoclonal antibody; D000910:Antibodies, Heterophile; D000911:Antibodies, Monoclonal; D015021:Yttrium Radioisotopes