A clinical trial of radioimmunotherapy with Cu-67-2IT-BAT-Lym-1 for non-Hodgkin's lymphoma

Encouraged by the results of I-131-Lym-1 therapy trials for patients with B -cell non-Hodgkin's lymphoma (NHL), this phase I/II clinical trial of Cu-67 -2IT-BAT-Lym-1 was conducted in an effort to further improve the therapeuti c index of Lym-1-based radioimmunotherapy. Lym-1 is a mouse monoclonal anti body that preferentially targets malignant lymphocytes. Cu-67 has beta emis sions comparable to those of I-131 but has gamma emissions more favorable f or imaging. The macrocyclic chelating agent 1,4,7,11-tetraazacycloletradeca ne-N,N',N ",N'''-tetraacetic acid binds Cu-67 tightly to form a stable radi oimmunoconjugate in vivo. Methods: All 12 patients had stage III or IV NHL that had not responded to standard therapy; 11 had intermediate- or high-gr ade NHL. At 4-wk intervals, patients received up to four doses of Cu-67-2IT -BAT-Lym-1, 0.93 or 1.85-2.22 GBq/m(2) (25 or 50-60 mCi/m(2)), with the low er dose used when NHL was detected in the bone marrow. Results: Cu-67-2IT-B AT-Lym-1 provided good imaging of NHL and favorable radiation dosimetry. Th e mean radiation ratios of tumor to body and tumor to marrow were 28:1 and 15:1, respectively. Tumor-re-lung, -kidney and -liver radiation dose ratios were 7.4:1, 5.3:1 and 2.6:1, respectively. This Cu-67-2IT-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 toxic ity, especially thrombocytopenia, was dose limiting. Conclusion: 67Cu remai ns an option for future clinical trials. This study established Cu-67-2IT-B AT-Lym-1 as a safe, effective treatment for patients with NHL.