Retreatment with 90Y-labelled ibritumomab tiuxetan in a patient with follicular lymphoma who had previously responded to treatment

Abstract

The patient’s clinical history began in September, 2000, when he was aged 68 years, with a diagnosis of grade 1 follicular lymphoma with a bulky left inguinal presentation. He was treated with cyclophosphamide (600 mg/m2), doxorubicin (25 mg/m2), and teniposide (60 mg/m2) on day 1, and prednisolone (40 mg/m2) on days 1 to 5 (CHVP), given monthly for six cycles and then every 2 months for 1 year, plus interferon alfa-2b (5 million units three times weekly) for 18 months. At the end of this treatment, CT scans showed he was in complete remission and he remained so for 12 months. In May, 2003, the patient presented with B symptoms and supradiaphragmatic and infradiaphragmatic nodal invol ve ment. This relapse was treated with three cycles of induction immunochemotherapy with rituximab (375 mg/m2) on day 1, cisplatin (100 mg/m2) on day 1, cytarabine (2 g/12 h per m2) on day 2, and dexamethasone (40 mg/m2/day) on days 1−4 (R-DHAP). 18-fl uorodeoxyglucose-PET ([18F]FDG-PET) was done 2 months after the third cycle and did not show any residual disease. Subsequently, the patient underwent high-dose chemotherapy with carmustine (300 mg/m2) and etoposide (100 mg/m2) on days 2–5, cytarabine (100 mg/m2 twice daily) on days 2–5, and melphalan (140 mg/m2) on day 6 (BEAM) with autologous stem-cell transplantation as consolidative treatment in February, 2004. After a further [18F]FDG-PET assessment, he was deemed to be in complete remission; however, in September, 2004, an asymptomatic supra diaphragmatic and infradiaphragmatic nodal relapse was noted in a routine follow-up [18F]FDG-PET, after which, a watch-and-wait strategy was chosen. In December, 2004, a marked progression was confi rmed with further [18F]FDG-PET. A biopsy of a right inguinal node showed a grade 3 follicular lymphoma, which indicated a trans formation to a more aggressive histology than that of the initial one. Other investigations showed less than 20% involvement of bone marrow with lymphoma. Therefore, in March, 2005, a third-line treatment with 90-yttrium (90Y)-labelled ibritumomab tiuxetan was given (1025 MBq). 1 month later, a complete disease reassessment with [18F]FDG-PET showed a complete remission, which was maintained for 12 months. In March, 2006, the patient had a third relapse, which was detected by [18F]FDG-PET in a routine follow-up. The bone marrow was not involved and the blood-cell count was normal. Due to the eff ectiveness and longevity of the response to the previous treatment with 90Y-ibritumomab tiuxetan, retreatment with the same protocol was undertaken. Subsequent haematological toxicity was acceptable and similar to that noted after initial treatment. Toxic eff ects were: grade 3 or 4 neutropenia (<1 x 109 cells/L) lasting 40 days without infection; grade 3 or 4 thrombocytopenia (<50 x 109 cells/L) lasting 30 days without haemorrhagic syndrome; and grade 3 anaemia (haemoglobin <65–80 g/L), which needed two transfusions of red blood cells. Assessment of the response by [18F]FDG-PET, 45 days after the procedure, showed complete remission (fi gure). In September, 2006, 6 months after retreatment with 90Y-ibritumomab tiuxetan, the patient was still alive and free of disease. Radioimmunotherapy is especially useful for the treatment of follicular lymphoma because, in addition to promoting antitumour activity through anti-CD20 antibody-mediated mechanisms, it can target a patientspecifi c dose of radiation to the tumour with minimum toxicity to healthy organs. 90Y-ibritumomab tiuxetan is an immunoconjugate in which ibritumomab, a murine CD20 monoclonal antibody, is covalently bound to tiuxetan, a high-affi nity, linker-chelator for 90Y. Witzig and colleagues compared the effi cacy of 90Y-ibritumomab tiuxetan with that of rituximab monotherapy in a randomised phase III trial in patients with relapsed or refractory CD20+ B-cell non-Hodgkin lymphoma. 90Y-ibritumomab tiuxetan was especially eff ective in the 113 patients with follicular lymphoma, in whom the overall response was 86% (n=55), compared with 55% (n=58) for those in the rituximab group (p<0·001). Lancet Oncol 2007: 8: 849–50