A Phase II Trial of FM (Oral Fludarabine and Mitoxantrone) Chemotherapy Followed by Yttrium 90 (⁹⁰Y) Ibritumomab Tiuxetan (Zevalin®) for Previously Untreated Follicular Lymphoma (FL) Patients.

We conducted a prospective, multicenter, single-arm, open-label, non-randomized, phase II study to evaluate the efficacy and safety of ⁹⁰Y Ibritumomab Tiuxetan of a new approach combining induction chemotherapy with oral Fludarabine and Mitoxantrone (FM) followed by consolidation with ⁹⁰Y Ibritumomab Tiuxetan for patients with previously untreated FL. Patient eligibility was represented by: age ≥ 18 years with biopsy-proven, untreated; stage II – IV FL grade I–II; WHO performance status of 0 to 2. All patients signed a written informed consent. Patients were treated with standard FM chemotherapy (Fludarabine was administered orally at the dose 40 mg/m²/day for 3 consecutive days) every 28 days for 6 cycles. Patients were restaged 4 to 8 weeks after completion of the sixth cycle of FM. Patients achieving at least a PR after 6 cycles of FM chemotherapy were eligible for consolidation with ⁹⁰Y Ibritumomab Tiuxetan provided the granulocyte count was > 1500/μL, the platelet count >100.000/μL, lymphocytes expressing the CD20 antigen and the bone marrow examination at the completion of FM demonstrated < 25% involvement with lymphoma. All patients were to receive a single dose of ⁹⁰Y Ibritumomab Tiuxetan 14.8 MBq/kg (0.4 mCi/kg) up to a maximum dose of 1184 MBq (32 mCi). At data reporting for this abstract, 62 patients were enrolled and 41 were evaluable for response. Of these 41 patients, all are evaluable for induction FM regimen and 19 of them also are evaluable after ⁹⁰Y Ibritumomab Tiuxetan treatment. 15 were male and 26 female; the median age was 52.5 years (range 36–70); 5 were stage II, 12 stage III, and 24 stage IV. After the FM treatment the OR rate was 100%, including 73% complete remissions (CR + CRu) and 27% PR. Time to event analyses, including TTP and duration of response are pending further follow-up. Treatment was well tolerated; grade ≥ 3 AEs were seen in 20 patients; the most common grade ≥ 3 AEs was neutropenia. Among the actual 19 evaluable patients subsequentially treated with ⁹⁰Y Ibritumomab Tiuxetan, 3/5 (60%) patients improved their remission status from PR to CR. The ⁹⁰Y Ibritumomab Tiuxetan toxicity included grade ≥ 3 hematologic AEs in 12 patients. These preliminary data indicate: 1) FM regimen including oral fludarabine presents the same activity of i.v. formulation one without significant gastrointestinal toxicity and with a better patient compliance; 2) feasibility, tolerability, and efficacy of the FM plus ⁹⁰Y Ibritumomab Tiuxetan regimen for untreated FL. Final efficacy and safety data will be presented.