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CME Evaluation

Oral Communication Session

Platelet Disorders

Session: TTP: Animal model to real-world data

OC 26.2 - Bortezomib for rituximab-refractory immune-mediated thrombotic thrombocytopenic purpura in the caplacizumab era: update of an Italian multicenter study

Sunday, June 23, 2024
15:00 – 15:15 ICT
Room: 111 A-C

    Presenting Author(s)

  • Juri Alessandro Giannotta, Medical Doctor

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

  • IM

    Ilaria Mancini

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

  • MC

    Monica Carpenedo

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

  • Addolorata Truma, MD

    Research fellow
    Università degli studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy.
    milano, Lombardia, Italy

  • Pasquale Agosti, MD, PhD

    Assistant Professor Clinician
    Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy.
    Milan, Lombardia, Italy

  • BF

    Barbara Ferrari

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

  • PD

    Pasqualina De Leo

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

  • PS

    Prassede Salutari

    MD
    Hematology Unit, Department of Oncology and Hematology, Spirito Santo Hospital, Pescara, Italy
    Pescara, Abruzzi, Italy

  • GM

    Giorgia Mancini

    MD
    Hematological Unit, Polytechnic Marche University, Ancona, Italy
    Ancona, Marche, Italy

  • AM

    Alfredo Molteni

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

  • ER

    Erminia Rinaldi

    MD
    Hematology Unit, A. Perrino Hospital, Brindisi, Italy
    Brindisi, Puglia, Italy

  • MB

    Monica Bocchia

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

  • Mariasanta Napolitano

    MD
    PROMISE Department, University of Palermo, Palermo, Italy
    Palermo, Sicilia, Italy

  • LP

    Lucia Prezioso

    MD
    Hematology and BMT Unit, Azienda Ospedaliero-Universitaria di Parma, 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 Department and Transfusion Service, Castelfranco Veneto Regional Hospital, Castelfranco Veneto, Italy
    Castelfranco Veneto, Veneto, Italy

  • AC

    Annalisa Condorelli

    MD
    Department of Hematology, ASST Papa Giovanni XXIII, Bergamo, Italy
    Bergamo, Lombardia, Italy

  • DG

    Daniele Grimaldi

    MD
    Hematology Division, AO S. Croce e Carle, Cuneo, Italy
    Cuneo, Piemonte, Italy

  • Flora Peyvandi, MD, PhD

    Full Professor
    Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Università degli Studi di Milano, Department of Pathophysiology and Transplantation
    Milan, Lombardia, Italy

Background: About 10% of immune-mediated thrombotic thrombocytopenic purpura (iTTP) patients are refractory to standard immunosuppressants (IS). The use of bortezomib in this setting appears promising, but data are limited and predate the caplacizumab era. We previously reported on the Italian experience with bortezomib at ISTH 2023.

Aims: To evaluate safety and efficacy of bortezomib in an expanded cohort of rituximab-refractory iTTP patients.

Methods: Adult iTTP treated with bortezomib in the acute phase/pre-emptively and regularly followed-up were enrolled from May-2017 to June-2023 at 13 Italian iTTP-treating centers after obtaining informed consent.

Results: Seventeen consecutive patients, 10 of whom refractory also to other IS than rituximab (Table 1), underwent 19 treatments with bortezomib: 11 were administered during/after the acute phase (6/11 during caplacizumab treatment) and 8 during clinical remission. Bortezomib was effective in 11/19 treatments (10/17 patients, Table 2): 9/11 treatments in the acute phase (5 ADAMTS13 complete remissions, 3 ADAMTS13 partial remissions, allowing caplacizumab discontinuation, and 1 reduction in plasma exchange frequency) and 2/8 treatments during clinical remission (ADAMTS13 complete remission). Median time to response was 30 days (IQR 113); three patients responded after 4 months. The median duration of response was 22 months (IQR 28), with 6 patients still responding at the time of writing. Responders had had fewer iTTP episodes than non-responders (median [IQR] 1.5 [1] vs 5 [5], respectively, p< 0.03). Seven subjects (41%) reported toxicities, mostly paraesthesia.

Conclusion(s): We confirmed durable responses to bortezomib in about 60% of multi-refractory iTTP patients, with common but generally manageable toxicities. We observed a higher response rate in the acute phase and at disease onset/first relapse, suggesting its use in these settings. Notably, bortezomib responders were able to discontinue caplacizumab, administered for >2 months in some patients, thus providing safety and pharmacoeconomic advantages. The occurrence of late responses suggests a “watchful waiting” approach following bortezomib treatment.