Italian real life experience with ibrutinib: results of a large observational study on 77 relapsed/refractory mantle cell lymphoma

// Alessandro Broccoli 1 , Beatrice Casadei 1 , Alice Morigi 1 , Federico Sottotetti 2 , Manuel Gotti 3 , Michele Spina 4 , Stefano Volpetti 5 , Simone Ferrero 6 , Francesco Spina 7 , Francesco Pisani 8 , Michele Merli 9 , Carlo Visco 10 , Rossella Paolini 11 , Vittorio Ruggero Zilioli 12 , Luca Baldini 13 , Nicola Di Renzo 14 , Patrizia Tosi 15 , Nicola Cascavilla 16 , Stefano Molica 17 , Fiorella Ilariucci 18 , Gian Matteo Rigolin 19 , Francesco D'Alò 20 , Anna Vanazzi 21 , Elisa Santambrogio 22 , Roberto Marasca 23 , Lucia Mastrullo 24 , Claudia Castellino 25 , Giovanni Desabbata 26 , Ilaria Scortechini 27 , Livio Trentin 28 , Lucia Morello 29 , Lisa Argnani 1 and Pier Luigi Zinzani 1 1 Institute of Hematology "L. e A. Seràgnoli", University of Bologna, Bologna, Italy 2 Operative Unit of Medical Oncology, IRCCS Fondazione Maugeri, Pavia, Italy 3 Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy 4 Division of Medical Oncology A, National Cancer Institute, Aviano, Italy 5 Department of Hematology, DISM, Azienda Sanitaria Universitaria Integrata, Udine, Italy 6 Division of Hematology, Department of Molecular Biotechnologies and Scienze for Health, University Torino, Torino, Italy 7 Unit of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy 8 Hematology and Transplantation Unit, Regina Elena National Cancer Institute, Roma, Italy 9 Unit of Hematology, Ospedale di Circolo, Fondazione Macchi, Varese, Italy 10 Department of Cell Therapy and Hematology, San Bortolo Hospital, Vicenza, Italy 11 Hematology Service, Medicine Department, Rovigo Hospital, Rovigo, Italy 12 Division of Hematology, Niguarda Ca’ Granda Hospital, Milano, Italy 13 OncoHematology Unit, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, Milano, Italy 14 Unit of Hematology, Vito Fazzi Hospital, Lecce, Italy 15 Hematology Unit, Infermi Hospital Rimini, Rimini, Italy 16 IRCCS, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy 17 Unit of Oncology/Hematology, Azienda Ospedaliera "Pugliese-Ciaccio", Catanzaro, Italy 18 Unit of Hematology, Arcispedale Santa Maria Nuova di Reggio Emilia, Reggio Emilia, Italy 19 Unit of Hematology, Azienda Ospedaliero-Universitaria di Ferrara, Ferrara, Italy 20 Institute of Hematology, Università Cattolica del Sacro Cuore, Roma, Italy 21 Hemato-Oncology Division, European Institute of Oncology, Milano, Italy 22 Unit of Hematology, University-Hospital Città della Salute e della Scienza di Torino, Torino, Italy 23 Department of Medical Sciences, Hematology Unit, University of Modena and Reggio Emilia, Modena, Italy 24 Unit of Hematology, Ospedale San Gennaro di Napoli, Napoli, Italy 25 Unit of Hematology, Ospedale Santa Croce E Carle, Cuneo, Italy 26 Ematologia Clinica, Ospedale Maggiore, Trieste, Italy 27 Clinica di Ematologia Ospedali Riuniti, Ancona, Italy 28 Unit of Hematology, University of Padova, Padova, Italy 29 Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano, Italy Correspondence to: Pier Luigi Zinzani, email: pierluigi.zinzani@unibo.it Keywords: ibrutinib; mantle cell lymphoma; relapsed; refractory; real life Received: January 30, 2018      Accepted: April 07, 2018      Published: May 04, 2018 ABSTRACT Although sometimes presenting as an indolent lymphoma, mantle cell lymphoma (MCL) is an aggressive disease, hardly curable with standard chemo-immunotherapy. Current approaches have greatly improved patients’ outcomes, nevertheless the disease is still characterized by high relapse rates. Before approval by EMA, Italian patients with relapsed/refractory MCL were granted ibrutinib early access through a Named Patient Program (NPP). An observational, retrospective, multicenter study was conducted. Seventy-seven heavily pretreated patients were enrolled. At the end of therapy there were 14 complete responses and 14 partial responses, leading to an overall response rate of 36.4%. At 40 months overall survival was 37.8% and progression free survival was 30%; disease free survival was 78.6% at 4 years: 11/14 patients are in continuous complete response with a median of 36 months of follow up. Hematological toxicities were manageable, and main extra-hematological toxicities were diarrhea (9.4%) and lung infections (9.0%). Overall, 4 (5.2%) atrial fibrillations and 3 (3.9%) hemorrhagic syndromes occurred. In conclusions, thrombocytopenia, diarrhea and lung infections are the relevant adverse events to be clinically focused on; regarding effectiveness, ibrutinib is confirmed to be a valid option for refractory/relapsed MCL also in a clinical setting mimicking the real world.