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A Clinical Trial of Radioimmunotherapy with ⁶⁷Cu-21T-BAT-Lym-1 for Non-Hodgkin's Lymphoma

Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis Medical Center, Sacramento, California

Correspondence: For correspondence or reprints contact: Robert T. O'Donnell, MD, PhD, Molecular Cancer Institute, 1508 Alhambra Blvd., Ste. 3100, Sacramento, CA 95816.

ABSTRACT

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-21T-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. Conclusion: 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.

Key Words: antibody • ⁶⁷Cu • immunotherapy • lymphoma • radiotherapy

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