Radioimmunotherapy (RIT) of Refractory or Relapsed Hodgkin’s Lymphoma (HL) with ⁹⁰Yttrium-Labelled Antiferritin Antibody.

The aim of this study was to evaluate the safety and efficacy of radiolabelled DTPA-chelated rabbit polyclonal antiferritin antibody (Ab) in relapsed or refractory HL. The protocol included a first intravenous injection of ¹¹¹Indium-labelled antiferritin Ab followed by immunoscintigraphy at 4, 48, and 72 hours and intravenous injection of ⁹⁰Yttrium-labelled antiferritin Ab in the case of tumour targeting. Ten patients were included in the study: median number of chemotherapy regimens: 3; number of autografted pts: 8; number of previously irradiated pts: 9; response to last chemotherapy: 6 PR and 4 progressions. All immunoscintigraphies showed tumour targeting. Nine patients were treated, as the last patient died from progressive HL before therapeutic injection. Median injected activity was 12 MBq/kg (0.32 mCi/kg). Among the ten patients who were included in the study, 1 CR and 6 PR were observed (ORR 70%) with a median duration of response of 8 months (range: 7–12 months). Toxicity was mainly haematological, with grade 1 or 2 neutropenia and anaemia, and grade 2 and 3 thrombocytopenia. The pharmacokinetic study showed that the half-lives of ¹¹¹Indium and ⁹⁰Yttrium were almost identical. These results confirm those previously reported in the literature and show the therapeutic potential of rabbit polyclonal antiferritin Ab in relapsed or refractory HL. On the basis of all these results, MATBioPharma proposed to test a radioimmunotherapy with polyclonal antiferritin antibodies (Abs) in patients with refractory or relapsed HL. The treatment is constituted with chelated rabbit polyclonal antiferritin Abs to be loaded with ¹¹¹Indium for the diagnosis of the tumour(s) by immunoscintigraphy and with ⁹⁰Yttrium for the treatment of the tumour(s). A phase I study is still ongoing at the Institut Curie / Centre René Huguenin (France) to evaluate the safety and tolerability of ascending doses of ⁹⁰Yttrium antiferritin until the maximum tolerated dose (MTD) is reached and to select a dose for further investigation (one dose step below MTD). A pharmacokinetics is concomitantly performed to determine dose linearity and pharmacokinetic parameters of increasing ⁹⁰Y-Ab and Ab. The second dose level will be completed in the third quarter 2007 and available data on immunoscintigraphy, safety, and efficacy of included HL patients will be provided for the 49^th ASH congress.