Radioimmunotherapy with ¹⁷⁷Lu-DOTA-Rituximab: Final Results of a Phase I/II Study in 31 Patients with Relapsing Follicular, Mantle Cell, and Other Indolent B-Cell Lymphomas

The aim of this study was to determine the maximum tolerated dose (MTD) and to explore the clinical response to ¹⁷⁷Lu-DOTA-rituximab in the treatment of patients with relapsed follicular, mantle cell, or other indolent lymphomas such as marginal zone lymphoma. Methods: To evaluate the MTD, we adjusted the dosage of the radiopharmaceutical according to body surface area (BSA). Results: The MTD using ¹⁷⁷Lu-DOTA-rituximab was 1,665 MBq/m² of BSA. Thrombocytopenia and leukopenia were the dose-limiting toxicities. Significant anemia occurred only at dose level 7 (1,850 MBq/m² of BSA). We observed the nadir of platelets after a median of 36 d from treatment and the nadir of granulocytes after a median of 50 d. Median time to recovery to the next lower grade of toxicity was 7 d. Nonhematologic toxicity was negligible. We observed clinical responses at all dose levels and for all lymphoma entities. Some of the responses were durable; the longest follow-up is currently over 8 y. At present, 11 patients are alive and 8 patients are disease-free. Conclusion: Our results demonstrate the safety and feasibility of ¹⁷⁷Lu-DOTA-rituximab treatment for the lymphoma entities tested in this study.