Cancers (Dec 2021)
Efficacy of Front-Line Ibrutinib and Rituximab Combination and the Impact of Treatment Discontinuation in Unfit Patients with Chronic Lymphocytic Leukemia: Results of the Gimema LLC1114 Study
- Francesca Romana Mauro,
- Francesca Paoloni,
- Stefano Molica,
- Gianluigi Reda,
- Livio Trentin,
- Paolo Sportoletti,
- Monia Marchetti,
- Daniela Pietrasanta,
- Roberto Marasca,
- Gianluca Gaidano,
- Marta Coscia,
- Caterina Stelitano,
- Donato Mannina,
- Nicola Di Renzo,
- Fiorella Ilariucci,
- Anna Marina Liberati,
- Lorella Orsucci,
- Francesca Re,
- Monica Tani,
- Gerardo Musuraca,
- Daniela Gottardi,
- Pier Luigi Zinzani,
- Alessandro Gozzetti,
- Annalia Molinari,
- Massimo Gentile,
- Annalisa Chiarenza,
- Luca Laurenti,
- Marzia Varettoni,
- Adalberto Ibatici,
- Roberta Murru,
- Valeria Ruocco,
- Ilaria Del Giudice,
- Maria Stefania De Propris,
- Irene Della Starza,
- Sara Raponi,
- Mauro Nanni,
- Paola Fazi,
- Antonino Neri,
- Anna Guarini,
- Gian Matteo Rigolin,
- Alfonso Piciocchi,
- Antonio Cuneo,
- Robin Foà
Affiliations
- Francesca Romana Mauro
- Hematology, Department of Translational and Precision Medicine, Sapienza University, Via Benevento 6, 00161 Rome, Italy
- Francesca Paoloni
- GIMEMA Foundation, 00187 Rome, Italy
- Stefano Molica
- Department of Hematology, Pugliese Ciaccio Hospital, 88100 Catanzaro, Italy
- Gianluigi Reda
- Hematology Department, Foundation IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, University of Milan, 20100 Milan, Italy
- Livio Trentin
- Hematology Division, Department of Medicine, University of Padua, 35128 Padua, Italy
- Paolo Sportoletti
- Institute of Hematology-Centro di Ricerca Emato-Oncologica (CREO), Department of Medicine, University of Perugia, 06129 Perugia, Italy
- Monia Marchetti
- Department of Hematology, SS. Antonio e Biagio e Cesare Arrigo Hospital and University of Eastern Piedmont, 15121 Alessandria, Italy
- Daniela Pietrasanta
- Department of Hematology, Azienda Ospedaliera SS Arrigo e Biagio e Cesare Arrigo, 15121 Alessandria, Italy
- Roberto Marasca
- Hematology Unit, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, 41126 Modena, Italy
- Gianluca Gaidano
- Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, AOU Maggiore della Carità, 28100 Novara, Italy
- Marta Coscia
- Division of Hematology, A.O.U. Città della Salute e della Scienza di Torino and Department of Molecular Biotechnology and Health Sciences, University of Torino, 10100 Torino, Italy
- Caterina Stelitano
- Department of Hematology, Azienda Ospedaliera Bianchi Melacrino Morelli, 89124 Reggio Calabria, Italy
- Donato Mannina
- Division of Hematology, Azienda Ospedaliera Papardo, 98158 Messina, Italy
- Nicola Di Renzo
- Hematology and Stem Cell Transplant Unit, “Vito Fazzi” Hospital, 73100 Lecce, Italy
- Fiorella Ilariucci
- Hematology, Azienda Ospedaliera Arcispedale Santa Maria Nuova IRCCS, 42123 Reggio Emilia, Italy
- Anna Marina Liberati
- Department of Hematology, Università degli Studi di Perugia, A.O.S., 05100 Terni, Italy
- Lorella Orsucci
- Department of Hematology, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, 10100 Torino, Italy
- Francesca Re
- Hematology and Bone Marrow Transplant Center, Azienda Ospedaliera Universitaria di Parma, 43126 Parma, Italy
- Monica Tani
- Division of Hematology, Santa Maria delle Croci Hospital, 48121 Ravenna, Italy
- Gerardo Musuraca
- Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori-IRST, 47014 Meldola, Italy
- Daniela Gottardi
- A.O.U. S. Giovanni Battista A.O. Mauriziano-Umberto I, 10128 Torino, Italy
- Pier Luigi Zinzani
- IRCCS Azienda Ospedaliero-Universitaria di Bologna-Istituto di Ematologia “Seràgnoli” and Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, 40138 Bologna, Italy
- Alessandro Gozzetti
- Hematology, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy
- Annalia Molinari
- Department of Oncology and Hematology, Infermi Hospital, 47923 Rimini, Italy
- Massimo Gentile
- Hematology Section, Cosenza Hospital, 87100 Cosenza, Italy
- Annalisa Chiarenza
- Division of Haematology, Azienda Policlinico-OVE, 95123 Catania, Italy
- Luca Laurenti
- Fondazione Policlinico Universitario A Gemelli, IRCCS, 00168 Rome, Italy
- Marzia Varettoni
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
- Adalberto Ibatici
- U.O. Ematologia e Centro Trapianti di Midollo, Policlinico San Martino, 16132 Genova, Italy
- Roberta Murru
- Hematology and Stem Cell Transplantation Unit, Ospedale A. Businco, ARNAS “G. Brotzu”, 34121 Cagliari, Italy
- Valeria Ruocco
- Hematology, Department of Translational and Precision Medicine, Sapienza University, Via Benevento 6, 00161 Rome, Italy
- Ilaria Del Giudice
- Hematology, Department of Translational and Precision Medicine, Sapienza University, Via Benevento 6, 00161 Rome, Italy
- Maria Stefania De Propris
- Hematology, Department of Translational and Precision Medicine, Sapienza University, Via Benevento 6, 00161 Rome, Italy
- Irene Della Starza
- Hematology, Department of Translational and Precision Medicine, Sapienza University, Via Benevento 6, 00161 Rome, Italy
- Sara Raponi
- Hematology, Department of Translational and Precision Medicine, Sapienza University, Via Benevento 6, 00161 Rome, Italy
- Mauro Nanni
- Hematology, Department of Translational and Precision Medicine, Sapienza University, Via Benevento 6, 00161 Rome, Italy
- Paola Fazi
- GIMEMA Foundation, 00187 Rome, Italy
- Antonino Neri
- Hematology Department, Foundation IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, University of Milan, 20100 Milan, Italy
- Anna Guarini
- Hematology, Department of Translational and Precision Medicine, Sapienza University, Via Benevento 6, 00161 Rome, Italy
- Gian Matteo Rigolin
- Hematology Section, St. Anna University Hospital, 44121 Ferrara, Italy
- Alfonso Piciocchi
- GIMEMA Foundation, 00187 Rome, Italy
- Antonio Cuneo
- Hematology Section, St. Anna University Hospital, 44121 Ferrara, Italy
- Robin Foà
- Hematology, Department of Translational and Precision Medicine, Sapienza University, Via Benevento 6, 00161 Rome, Italy
- DOI
- https://doi.org/10.3390/cancers14010207
- Journal volume & issue
-
Vol. 14,
no. 1
p. 207
Abstract
The GIMEMA group investigated the efficacy, safety, and rates of discontinuations of the ibrutinib and rituximab regimen in previously untreated and unfit patients with chronic lymphocytic leukemia (CLL). Treatment consisted of ibrutinib, 420 mg daily, and until disease progression, and rituximab (375 mg/sqm, given weekly on week 1–4 of month 1 and day 1 of months 2–6). This study included 146 patients with a median age of 73 years, with IGHV unmutated in 56.9% and TP53 disrupted in 22.2%. The OR, CR, and 48-month PFS rates were 87%, 22.6%, and 77%, respectively. Responses with undetectable MRD were observed in 6.2% of all patients and 27% of CR patients. TP53 disruption (HR 2.47; p = 0.03) and B-symptoms (HR 2.91; p = 0.02) showed a significant and independent impact on PFS. The 48-month cumulative rates of treatment discontinuations due to disease progression (DP) or adverse events (AEs) were 5.6% and 29.1%, respectively. AEs leading more frequently to treatment discontinuation were atrial fibrillation in 8% of patients, infections in 8%, and non-skin cancers in 6%. Discontinuation rates due to AEs were higher in male patients (HR: 0.46; p = 0.05), patients aged ≥70 years (HR 5.43, p = 0.0017), and were managed at centers that enrolled p = 0.04). Patients who discontinued ibrutinib due to an AE showed a 24-month next treatment-free survival rate of 63%. In conclusion, ibrutinib and rituximab combination was an effective front-line treatment with sustained disease control in more than half of unfit patients with CLL. Careful monitoring is recommended to prevent and manage AEs in this patient population.
Keywords