A clinical trial of radioimmunotherapy with 67Cu-2IT-BAT-Lym-1 for non-Hodgkin's lymphoma.
Encouraged by the results of 131I-Lym-1 therapy trials for patients with B-cell non-Hodgkin's lymphoma (NHL), this phase I/II clinical trial of 67Cu-2IT-BAT-Lym-1 was conducted in an effort to further improve the therapeutic index of Lym-1-based radioimmunotherapy. Lym-1 is a mouse monoclonal antibody that preferentially targets malignant lymphocytes. 67Cu has beta emissions comparable to those of 131I but has gamma emissions more favorable for imaging. The macrocyclic chelating agent 1,4,7,11-tetraazacyclotetradecane-N,N',N",N"'-tetraacetic acid binds 67Cu tightly to form a stable radioimmunoconjugate in vivo.


METHODS
All 12 patients had stage III or IV NHL that had not responded to standard therapy; 11 had intermediate- or high-grade NHL. At 4-wk intervals, patients received up to four doses of 67Cu-2IT-BAT-Lym-1, 0.93 or 1.85-2.22 GBq/m2 (25 or 50-60 mCi/m2), with the lower dose used when NHL was detected in the bone marrow.


RESULTS
67Cu-2IT-BAT-Lym-1 provided good imaging of NHL and favorable radiation dosimetry. The mean radiation ratios of tumor to body and tumor to marrow were 28:1 and 15:1, respectively. Tumor-to-lung, -kidney and -liver radiation dose ratios were 7.4:1, 5.3:1 and 2.6: 1, respectively. This 67Cu-2IT-BAT-Lym-1 trial for patients with chemotherapy-resistant NHL had a response rate of 58% (7/12). No significant nonhematologic toxicity was observed. Hematologic toxicity, especially thrombocytopenia, was dose limiting.


CONCLUSIONS
67Cu remains an option for future clinical trials. This study established 67Cu-2IT-BAT-Lym-1 as a safe, effective treatment for patients with NHL.
O'Donnell
R T
RT
Department of Internal Medicine, University of California Davis Medical Center, Sacramento, USA.
DeNardo
G L
GL
Kukis
D L
DL
Lamborn
K R
KR
Shen
S
S
Yuan
A
A
Goldstein
D S
DS
Carr
C E
CE
Mirick
G R
GR
DeNardo
S J
SJ
D001853:Bone Marrow / Q000528:radiation effects; D005260:Female; D006571:Heterocyclic Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D016499:Radioimmunotherapy; D011879:Radiotherapy Dosage
D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C097568:copper-67-2IT-BAT-Lym-1