Phase I Trial of the 131I-Labelled Anti-CD25 Antibody Basiliximab in the Treatment of Patients with Relapsed or Refractory Lymphoma

Autor: Surinder K. Sharma, T. A. Lister, Pei-San Chan, A J Green, Christopher McNamara, Anmol Malhotra, Richard H. J. Begent, Ros Francis, Sweta Parker, Peter Amlot, Nicholas Woodward, Shokri Othman, John R. Buscombe, Peter G. Isaacson, John Violet, Natalie Griffin, Gairin Dancey
Rok vydání: 2007
Předmět:
Zdroj: Blood. 110:648-648
ISSN: 1528-0020
0006-4971
Popis: The survival of patients with Hodgkin lymphoma (HL) has improved over recent decades due to advances in therapy and supportive care. The outcome for patients with relapsed or refractory disease, however, is still unsatisfactory. High dose therapy with stem cell support can salvage many patients but results are poor in patients with chemo-resistant, PET-positive disease pre-transplant. Novel therapies for HL have focused on monoclonal antibodies to antigens such as CD30 but these treatments have produced response rates of only 10% when given as native antibody. Radio-immunotherapy is effective treatment for a range of lymphoproliferative disorders including those that are resistant to other therapies. This phase I study utilised basiliximab, a chimeric antibody to the α-chain of the IL-2 receptor, CD25, conjugated to iodine-131 (131I) in patients with relapsed or refractory lymphomas who were resistant to or intolerant of conventional therapies and who had demonstrable CD25 expression by immunohistochemistry on tissue sections. To determine dose-limiting toxicity an accelerated titration design was used with 6 different doses employed- 370, 740, 1480, 2220 and 2960MBq/m2. Fourteen patients (9M, 5F) with a median age of 38 years (range 28–70) were treated (HL 11 patients, primary mediastinal B-cell lymphoma 1, peripheral T-cell lymphoma NOS 1, adult T-cell leukaemia/lymphoma 1). They had previously received a median of 4 therapies (range 2–8) including autologous stem cell transplant in 9 patients. Five patients were being considered for an autologous or allogeneic stem cell transplantation but had not demonstrated chemosensitivity with standard therapies. All patients were FDG-positive by PET prior to therapy. One patient had a complete response at 740MBq/m2. Six of 9 patients responded to therapy at a dose of 1200MBq/m2 or higher. There were 3 complete responses and 3 partial responses. Two of these patients who had previously not been considered for high dose therapy because of a lack of response have now proceeded to autologous or allogeneic transplant. At a clinically active dose of 1200MBq/m2 the only side effects seen were delayed myelotoxicity; the median platelet count nadir was 31x109/L(range 9–83) and was observed at a median of 38 days (range 33–53) following treatment. Neutropenia (median nadir 1.31x109/L, range 0.9–7.5) was also noted at a median of 53 days (range 37–65) following therapy. One patient was treated at a dose of 2960MBq/m2 and developed prolonged grade 4 neutropenia and thrombocytopenia requiring stem cell support. The patient died of pneumocystis carinii pneumonia. There were no other grade 3 or 4 non-haematologic toxicities noted. The 131I-labelled anti-CD25 antibody basiliximab is well tolerated at doses of 1200MBq/m2 and demonstrates clinical activity at this dose in patients who are refractory to conventional therapies. Further studies are required to determine the long term outcome of patients treated with this agent and to assess its efficacy in the pre-autograft/allograft setting.
Databáze: OpenAIRE
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