Radioimmunotherapy with Tenarad, a 131I-labelled antibody fragment targeting the extra-domain A1 of tenascin-C, in patients with refractory Hodgkin's lymphoma
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The extra-domain A1 of tenascin-C (TC-A1) is highly expressed in the extracellular matrix of tumours and on newly formed blood vessels and is thus a valuable target for radionuclide therapy. Tenarad is a fully human miniantibody or small immunoprotein (SIP, molecular weight 80 kDa) labelled with 131I that is derived from a TC-A1-binding antibody. Previous phase I/II studies with a similar compound (131I-L19SIP) used for radioimmunotherapy (RIT) have shown preliminary efficacy in a variety of cancer types. In this ongoing phase I/II trial, Tenarad was administered to patients with recurrent Hodgkin's lymphoma (HL) refractory to conventional treatments.
Eight patients (four men, four women; age range 19 – 41) were enrolled between April 2010 and March 2011. All patients had received a median of three previous lines of chemotherapy (range three to six) and seven had also undergone autologous stem cell transplantation (ASCT) or bone marrow transplantation. In addition, seven patients received external beam radiation. All patients had nodal disease, constitutional B symptoms and some showed extranodal disease in skeletal bone (four patients), lung (three), liver (two) and spleen (one). Baseline assessments included whole-body FDG PET with contrast-enhanced CT and diagnostic Tenarad planar and SPECT studies. Patients were considered eligible to receive a therapeutic dose of Tenarad (2.05 GBq/m2) if tumour uptake was more than four times higher than that of muscle.
All patients were eligible and received the therapeutic dose of Tenarad. Only one patient developed grade 4 thrombocytopenia and leucocytopenia, requiring hospitalization and therapeutic intervention. All other patients had haematological toxicity of grade 3 or lower, which resolved spontaneously. At the first response assessment (4 – 6 weeks after therapy), one patient showed a complete response, one showed a partial response (PR) and five had disease stabilization (SD). Five patients were given up to three repeated Tenarad treatments. One patient showed SD which then improved to a PR, three showed clinical benefit while maintaining SD and one patient showed disease progression.
Tenarad RIT is effective in chemorefractory HL and resulted in objective responses or clinical benefit in the majority of patients. Toxicity was acceptable despite the high load of prior treatments, previous ASCT and multiple Tenarad administrations. Further studies are planned to define the most effective schedule for this type of RIT in HL patients.
KeywordsHodgkin's lymphoma Radioimmunotherapy Dosimetry 131I Tenascin-C
Philogen SpA sponsored this work under a protocol approved by the internal review board of our institution.
Conflicts of interest
None of the authors from the Istituto Nazionale Tumori, Fondazione “G. Pascale”, Napoli, Italy, received compensation for this study and none declare conflicts of interest. The remaining authors (D.N., L.G. and H.D.M.) are shareholders or employees of the protocol sponsor, Philogen SpA.
- 1.Bauer K, Skoetz N, Monsef I, Engert A, Brillant C. Comparison of chemotherapy including escalated BEACOPP versus chemotherapy including ABVD for patients with early unfavourable or advanced stage Hodgkin lymphoma. Cochrane Database Syst Rev. 2011:(8):CD007941. doi: 10.1002/14651858.CD007941.pub2
- 5.Horning S, Fanale M, deVos S, Borchmann P, Illidge T, Engert A, et al. Defining a population of Hodgkin lymphoma patients for novel therapeutics: an international effort [abstract 118]. Ann Oncol. 2008;19 Suppl 4:120–1Google Scholar
- 6.Younes A. Novel treatment strategies for patients with relapsed classical Hodgkin lymphoma. Hematology Am Soc Hematol Educ Program. 2009:507–19. doi: 10.1182/asheducation-2009.1.507
- 27.Aloj L, D’Ambrosio L, Aurilio M, Marreno R, Menssen HD, Giovannoni L, et al. Preliminary evaluation of radioimmunotherapy with Tenarad, a I-131 labeled antibody fragment targeting the extra-domain A1 of tenascin-C, in patients with refractory Hodgkin lymphoma. Journal of Clinical Oncology, 2011 ASCO Annual Meeting Abstracts. Vol 29, No. 15 suppl, 8063; 2011.Google Scholar