A Phase II Trial of R-FM (Rituximab, Fludarabine and Mitoxantrone) Chemotherapy Followed by Yttrium 90 (⁹⁰Y) Ibritumomab Tiuxetan (⁹⁰Y-IT) for Untreated Follicular Lymphoma (FL) Patients.

In 2008 we published a multicenter non-randomized phase II trial of fludarabine and mitoxantrone plus ⁹⁰Y-IT in untreated patients with FL. By the end of the entire treatment regimen 95% of the patients achieved complete remission (CR). With a median follow-up of 30 months, 3-year PFS was estimated to be 76% and 3-year OS 100%. On the basis of these results we are currently conducting a prospective, multicenter, non-randomized, phase II study of R-FM followed by ⁹⁰Y-IT in untreated patients with FL in which the number of fludarabine and mitoxantrone cycles has been decreased to four and in which rituximab is administered before each cycle. The rationale of the trial is to use different forms of treatment and to reduce the use of conventional chemotherapy and its related toxic effects.

Patients eligibility is represented by: age more than 18, stage II-IV, FL grade I-II, WHO performance status 0-2. Patients are treated with standard FM chemotherapy plus rituximab every 28 days for 4 cycles. Patients are restaged 4 to 8 weeks after completion of immunochemotherapy and those achieving at least a partial response are eligible for ⁹⁰Y-IT. All patients receive a single dose of ⁹⁰Y-IT 14,8 MBq/kg. At the time of the analysis we enrolled 55 patients. 25 patients were male and 30 female; the median age was 56 years (range 26-84); 12 patients were stage II, 13 stage III and 30 stage IV; 11 patients had a bulky disease. 52 patients completed the induction chemotherapy, all except 5 were eligible for the consolidation treatment with ⁹⁰Y-IT and 44 patients were restaged after the entire treatment regimen.

After the R-FM chemotherapy, the overall response rate was 92.3% (48/52) including 39 (75%) CR and 9 (17.3%) partial remissions (PR). Time to event analyses, including TTP and duration of response are pending further follow-up. Treatment was well tolerated grade 3-4 haematologic AEs (mostly neutropenia) were seen in 50% of the patients. Among the 44 patients (9 PR and 35 CR) subsequentially treated with ⁹⁰Y-IT and reassessed for the response, 8/9 (88.9%) PR patients improved their remission status from PR to CR. ⁹⁰Y-IT toxicity included mostly grade 3-4 neutropenia and thrombocytopenia and was comparable to the literature data.

These preliminary data indicate that radioimmunotherapy appears highly effective and feasible as “consolidation” after short (4 cycles) immunochemotherapy in FL patients, improving quality of response without any cumulative toxicity.

No relevant conflicts of interest to declare.