Efficacy and Safety of Yttrium 90 (⁹⁰Y) Ibritumomab Tiuxetan (Zevalin®) Therapy with Rituximab Maintenance in Patients with Untreated Low-Grade Follicular Lymphoma.

Background: Recent trials have demonstrated the efficacy of rituximab induction therapy, when followed by maintenance rituximab, in patients with untreated low-grade follicular NHL. Earlier studies, employing low-dose total-body irradiation as an initial treatment for follicular lymphoma (FL), have previously shown the inherent radiosensitivity of the disease. Based on these findings, we evaluated the efficacy and safety profile of frontline ⁹⁰Y ibritumomab tiuxetan (Zevalin^®) delivered prior to maintenance rituximab in patients with low-grade FL.

Methods: Patients were eligible for treatment if they presented with histologically confirmed, previously untreated low-grade FL. Additional eligibility criteria included stage III or IV disease and a need for therapeutic intervention because of constitutional symptoms, evidence of disease progression, or organ dysfunction directly attributable to NHL. Patients were excluded if there was evidence of histologic transformation to aggressive disease. On day 1, patients received an initial infusion of rituximab (250 mg/m²) followed by an imaging dose of Indium 111 (¹¹¹In) ibritumomab tiuxetan (5 mCi). One week later, a second infusion of rituximab (250 mg/m²) was given, proceeded by an injection of ⁹⁰Y ibritumomab tiuxetan (0.3 or 0.4 mCi/kg, depending upon platelet count). Rituximab maintenance therapy (375 mg/m² x 4) was scheduled at 6-month intervals over 2 years. Endpoints included clinical response rates using standard International Workshop Response Criteria (IWRC) and toxicity.

Results: Ten patients, presenting with grade I or II FL, have been treated with ⁹⁰Y ibritumomab tiuxetan, and 8 are evaluable for treatment response. The median age of patients was 58 years (range, 40–82) and 50% (5/10) of patients had stage IV disease. Delivered doses of ⁹⁰Y ibritumomab tiuxetan ranged from 21–32 mCi. Toxicities were primarily hematologic with grade 3 cytopenia occurring in 38% (3/8) of patients. Of the 8 patients qualifying for evaluation, 5 (62%) had complete responses and 3 (38%) had partial responses to ⁹⁰Y ibritumomab tiuxetan induction.

Conclusions: These data illustrate that frontline ⁹⁰Y ibritumomab tiuxetan therapy produces high rates of response (100% in this small population) in patients with low-grade FL. Toxicities following administration of radiolabeled antibody were manageable. Further follow-up is needed to determine the long-term efficacy of combining frontline radioimmunotherapy with antibody-based maintenance.