Efficacy and Safety of FCR (Fludarabine, Cyclophosphamide, Rituximab) Followed by Yttrium-90 Ibritumomab Tiuxetan in Relapsed Follicular Lymphoma (FL) Patients

Background: FCR regimen has provided encouraging results in FL and Yttrium-90 Ibritumomab Tiuxetan (⁹⁰Y-RIT) has been reported to be effective in patients with relapsed or refractory FL. Our study investigates the efficacy and safety of ⁹⁰Y-RIT consolidation in relapsed FL patients, responding to second-line with FCR.

Methods: At date reporting for this abstract we have recruited 10 patients median age 63 yrs (range 46–77). All enrolled patients were relapsed patients with histologically confirmed CD20-positive (grade 1 or 2) FL according to WHO classification. Major inclusion criteria were: age ≥ 18 years, WHO performance status of 0, 1 or 2, no prior therapy with Rituximab for 3 months and at the completion of FCR, patients achieving at least PR, with < 25% bone marrow involvement, with neutrophil count ≥ 1500/microlitre and platelet count ≥ 100000/microlitre. All patients at relapse received every 28 days FCR: F (25mg/m²×3 days), C (1gr/m²day1) and R (375mg/m²day4) for 4 cycles. Patients were restaged 4 to 8 weeks after the last course of FCR; who achieved at least a partial remission was eligible for Yttrium-90 Ibritumomab Tiuxetan 11.1 or 14.8 MBq/Kg (0.3–0.4 mCi/Kg) up to a maximum dose 1184 MBq at 3 months after the completion of FCR. The patients were restaged with total body CT scan, FDG-PET/CT and bilateral bone marrow biopsy at 4 to 8 weeks after the last cycle of FCR. A complete blood cell count was obtained once a week for 12 weeks after ⁹⁰Y-RIT treatment. A history and physical examination were performed together with renal and liver function once a months for 3 months after ⁹⁰Y-RIT. All patients received prophylaxis with trimethoprim-sulfamethoxazolo and valacyclovir from initiation of therapy until 3 ≥ months following therapy with ⁹⁰Y-RIT.

Results: Between August 2005 and March 2008 nine patients have completed the treatment: FCR followed by ⁹⁰Y-RIT (6 patients at 0.4 mCi/Kg, 3 patients at 0.3 mCi/Kg) and one patient is under treatment. All 10 patients were relapsed patients: 6 patients received 1 or 2 prior therapy regimens and 4 patients had received 3 to 5 regimens. Eight of them were previously treated with Rituximab plus chemotherapy, 2 patients had no previous Rituximab treatment history, one also had ABMT. After FCR 6 patients obtained CR and 3 PR; after ⁹⁰Y-RIT treatment the ORR was 100% and CCR was 100% with median follow up of 13 months (range 5–26) and all patients are alive in CR; 3 patients in PR after FCR regimen converted to CR by ⁹⁰Y-RIT. The most common grade 3 or 4 adverse events were hematologic: grade 3 or 4 neutropenia occurred in 10/10 patients treated with FCR and grade 3 or 4 neutropenia and thrombocytopenia in 9/9 patients assessable after ⁹⁰Y-RIT. Following treatment with ⁹⁰Y-RIT the median neutrophil nadir was 0.5 × 10⁹/L (range 0.3 – 1.09 ×10⁹/L) at week 5; the median platelet count nadir was 40 × 10⁹/L ( range 12–81 × 10⁹/L ) at week 6. One patient developed herpes zoster infection after 8 months following valacyclovir discontinuation; another patient developed fungus infection. No other severe infection have been recorded, no nonhematologic adverse event have been registered so far.

Conclusion: Our experience indicate feasibility, tolerability and efficacy of FCR regimen followed by ⁹⁰Y-RIT in patients relapsed with FL. Hematologic toxicity occurring with FCR or with radio-immunotherapy are clinically controllable and acceptable in the population composed mainly of patients with a history of prior treatment using rituximab plus chemotherapy. A longer follow up and a larger number of patients with relapsed FL are required to determine the impact of this regimen on long-term duration of response and EFS.