Is there need for radioimmunotherapy? results of a phase I/II study in patients with indolent B-cell lymphomas using lutetium-177-DOTA-rituximab.

AIM: The aim of the study was to explore the clinical response to 177Lutetium-DOTA-rituximab (177Lu-D-R) and to determine the maximum tolerated dose (MTD) in the treatment of patients with relapsed follicular, mantle cell or other indolent lymphomas such as marginal zone lymphoma as well as to put these results into context with other therapy options for these patients.

METHODS: Treatment consisted of cold rituximab (250 mg/m2) on day 1 and day 8 and 177Lu-DOTA-Rituximab on day 8. Reassessment was done at week 10. Thirty-one patients (males=17, females=14, median number of pretreatments: 3) were treated in seven cohorts. Escalation of injected activity was carried out in steps of 5 mCi/m². Dosimetry was performed in the first 20 patients.

RESULTS: The MTD was found to be 45 mCi/m2. Thrombocytopenia and leukopenia were the dose-limiting toxicities. Significant anemia only occurred at dose level 7. We observed the nadir of platelets after a median of 36 days from treatment with 177Lu-D-R and a nadir of granulocytes after a median of 50 days from 177Lu-D-R treatment. Non-hematological 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 in complete remission is currently over eight years.

CONCLUSION: The MTD of 177Lu-DOTA-Rituximab was found to be 45 mCi/m². Non hematologic toxicity was negligible. Responses were seen in all lymphoma entities and at all dose levels tested. Further testing seems to be most promising mainly in follicular and marginal zone lymphoma in particular as the results compare well to other therapy options for these patients with regard to effectiveness, toxicity and discomfort for the patients.