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

We conducted a prospective, single-arm, open-label, non-randomized, multicenter, phase II to evaluate the efficacy and safety of ⁹⁰Y Ibritumomab Tiuxetan of a novel new approach combining induction chemotherapy with Fludarabine and Mitoxantrone (FM) followed by consolidation with ⁹⁰Y Ibritumomab Tiuxetan for patients with previously untreated indolent non-follicular lymphoma (indolent non-FL). Patient eligibility was represented by: patients age 18 years or older with biopsy-proven, untreated, bidimensionally measurable stage II, stage III, or stage IV indolent non-FL expressing the CD20 antigen; WHO performance status of 0 to 2. All patients were notified of the investigational nature of this study and signed a written informed consent approved in accordance with institutional guidelines, including the Declaration of Helsinki. The study was approved by the institutional review boards. Patients were treated with standard FM chemotherapy every 28 days for 6 cycles. Patients were restaged 4 to 8 weeks after completion of the sixth cycle of FM chemotherapy. Patients achieving at least a partial response after 6 cycles of FM chemotherapy were eligible for consolidation with ⁹⁰Y Ibritumomab Tiuxetan provided the granulocyte count was greater than 1500/μL, the platelet count exceeded 100.000/μL, and the bone marrow examination at the completion of FM chemotherapy demonstrated no more than 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, 29 patients were enrolled and 26 were evaluable for response. Of these 26 patients, all are evaluable for induction chemotherapy FM regimen and 17 of them also are evaluable after ⁹⁰Y Ibritumomab Tiuxetan treatment. Histologically, 11 had marginal zone lymphoma, 10 had lymphoplasmacytic lymphoma, and 5 had small lymphocytic lymphoma; 10 were male and 16 female; the median age was 61 years (range 45–82); 4 were stage III, and 21 stage IV. After the FM treatment the overall response rate was 81%, including 50% CR and 31% 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 13 patients; the most common grade ≥ 3 AEs was neutropenia. Among the actual 17 evaluable patients subsequentially treated with ⁹⁰Y Ibritumomab Tiuxetan, 2/4 (50%) patients improved their remission status from PR to CR. The ⁹⁰Y Ibritumomab Tiuxetan toxicity included grade ≥ 3 hematologic AEs in 15 patients; the most common grade ≥ 3 AEs were neutropenia (10 patients) and thrombocytopenia (15 patients). Transfusions of red cells and/or platelets were given to 6 patients. These preliminary data indicate the feasibility, tolerability, and efficacy of the FM plus ⁹⁰Y Ibritumomab Tiuxetan regimen for patients with untreated indolent non-FL. Final efficacy and safety data will be presented.