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    Poster Networking

    Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies

    Poster Networking Session

    PB0316 - Bortezomib for the treatment of multi-refractory immune-mediated thrombotic thrombocytopenic purpura: an Italian multicenter survey

    Sunday, June 25, 2023
    18:30 – 19:30 ET
    Room: Exhibition

      Presenting Author(s)

    • Juri Alessandro Giannotta, MD

      Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
      Milano, Lombardia, Italy

      • Co-Author(s)

    • Andrea Artoni, MD

      MD
      Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
      Milano, Lombardia, Italy

    • IM

      Ilaria Mancini, PhD

      Post-Doc Research Fellow
      Università degli Studi di Milano, Department of Pathophysiology and Transplantation and Fondazione Luigi Villa, Milan, Italy
      Milan, Lombardia, Italy

    • Addolorata Truma, MD

      Resident doctor in Internal Medicine
      Università degli Studi di Milano, Department of Pathophysiology and Transplantation
      Milano, Lombardia, Italy

    • Pasquale Agosti, MD, PhD

      Università degli Studi di Milano, Department of Pathophysiology and Transplantation and Fondazione Luigi Villa, Milan, Italy
      Milano, Lombardia, Italy

    • MC

      Monica Carpenedo

      MD
      U.O.C. Ematologia e SIMT, ASST Fatebenefratelli-Sacco, Ospedale L. Sacco, Polo Didattico Università degli Studi di Milano, Milan, Italy
      Milano, Lombardia, Italy

    • GM

      Giorgia Mancini

      MD
      Clinica di Ematologia, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Torrette, Italy
      Ancona, Marche, Italy

    • AM

      Alfredo Molteni

      MD
      UOC Ematologia e CTMO, ASST Cremona
      Cremona, Lombardia, Italy

    • ER

      Erminia Rinaldi

      MD
      Haematology, A. Perrino Hospital, Brindisi, Italy
      Brindisi, Puglia, Italy

    • MB

      Monica Bocchia

      MD
      Hematology Unit, Azienda Ospedaliero Universitaria Senese, University of Siena
      Siena, Toscana, Italy

    • Mariasanta Napolitano, 310885

      Associate Professor of hematology
      Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), University of Palermo, Palermo, Italy
      Palerno, Sicilia, Italy

    • LP

      Lucia Prezioso

      MD
      U.O. Ematologia E Centro Trapianti Midollo Osseo, Ospedale Maggiore, Parma, Italy
      Parma, Emilia-Romagna, Italy

    • AC

      Annarosa Cuccaro

      MD
      Hematology Unit, Center for Translational Medicine, Azienda USL Toscana NordOvest, Livorno, Italy
      Livorno, Toscana, Italy

    • ES

      Elisabetta Scarpa

      MD
      Hematology Division, Treviso Hospital , Treviso, Italy
      Treviso, Veneto, Italy

    • DG

      Daniele Grimaldi

      MD
      Division of Hematology, A.O.S. Croce e Carle, Cuneo, Italy
      Cuneo, Piemonte, Italy

    • MM

      Massimo Massaia

      MD
      Division of Hematology, Santa Croce e Carle Hospital, Cuneo
      Cuneo, Piemonte, Italy

    • Flora Peyvandi, MD, PhD (she/her/hers)

      Director
      IRCCS Ca' Granda Maggiore Hospital Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy; Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milano, Italy
      Milano, Lombardia, Italy

    Background: About 10-15% of immune-mediated thrombotic thrombocytopenic purpura (iTTP) patients do not achieve a sustained response to standard treatment with plasma exchange (PEX), steroids, caplacizumab and rituximab, with unsatisfactory outcomes using traditional immunosuppressants (IST). In this setting, the employment of bortezomib, targeting the plasma cells responsible for rituximab-refractoriness, appears promising.

    Aims: To evaluate the safety and efficacy of bortezomib administered off-label in rituximab-refractory iTTP patients.

    Methods: We conducted a retrospective survey among 30 Italian iTTP-treating centers. Adult iTTP patients who received bortezomib in the acute phase or pre-emptively and regularly followed-up were enrolled after obtaining informed consent.

    Results: Twelve iTTP patients (50% females, median age 43 years, range 24-77) with a median follow-up of 4 years (0.5-17.4) were included (Table 1). Treatments prior to bortezomib included PEX, steroids, rituximab in all and additional IST in 5 subjects (cyclophosphamide in 4 and cyclosporine and mofetil mycophenolate in one). Eleven patients (one treated twice) had a sufficient follow-up period to allow evaluation (Table 2). Seven patients received bortezomib in the acute phase, and 5 pre-emptively. Response was achieved in 7/11 patients (64%): 6/7 in the acute phase (5 clinical remission, 3 of which with ADAMTS13 complete remission) and 2/5 treated pre-emptively (both obtaining ADAMTS13 complete remission). Responses occurred mostly within one month with a median duration of 24 months. Only two ADAMTS13 relapses were recorded among responders (one successfully retreated with bortezomib). Four subjects reported mild toxicities, mostly paresthesia.

    Conclusion(s): Fast and durable responses to bortezomib were registered in 64% of multi-refractory iTTP patients, without significant toxicities. The trend to a better response in the acute phase might suggest its use in this setting. Limitations include the use of concomitant therapies, the retrospective collection of data and the small sample size, although it is the largest reported so far. Prospective controlled studies are warranted.