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.

Follicular lymphoma (FL) has been considered as low-grade malignant B-cell lymphoma usually characterized by an indolent course with a continuous pattern of relapse and a median survival of 10 years. The therapeutic approach to FL is particularly controversial. One of the effective strategies is the combination of fludarabine-containing regimens (particularly, Fludarabine and Mitoxantrone) with anti-CD20 monoclonal antibody. Single-agent radioimmunotherapy activity, in particular Yttrium 90 (⁹⁰Y) Ibritumomab Tiuxetan (Zevalin), has been demonstrated in heavily pretreated FL patients. The results of these studies support a further evaluation of ⁹⁰Y Ibritumomab Tiuxetan in combination with chemotherapy earlier in the time course of FL. Recently, some phase II trials showed that the sequential combination of conventional chemotherapy (CHOP) and ⁹⁰Y Ibritumomab Tiuxetan has useful activity in the treatment of FL patients, with no unexpected toxicities observed. 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 oral Fludarabine and Mitoxantrone (FM) followed by consolidation with ⁹⁰Y Ibritumomab Tiuxetan for patients with previously untreated elderly 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 FL expressing the CD20 antigen; performance status of 0 to 2, a pretreatment granulocyte cell count of 1500/μL or greater, and a platelet count of 100.000/μL or greater. 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 board. Patients were treated with standard FM chemotherapy (in this case, Fludarabine was administered orally at the dose 40 mg/m²/day for 3 consecutive days) every 21 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 CHOP 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). A total of 60 patients have to be enrolled and preliminary results of this trial will be presented.