Haematologica (Jul 2018)
Efficacy of bendamustine and rituximab as first salvage treatment in chronic lymphocytic leukemia and indirect comparison with ibrutinib: a GIMEMA, ERIC and UK CLL FORUM study
- Antonio Cuneo,
- George Follows,
- Gian Matteo Rigolin,
- Alfonso Piciocchi,
- Alessandra Tedeschi,
- Livio Trentin,
- Angeles Medina Perez,
- Marta Coscia,
- Luca Laurenti,
- Gerardo Musuraca,
- Lucia Farina,
- Alfredo Rivas Delgado,
- Ester Maria Orlandi,
- Piero Galieni,
- Francesca Romana Mauro,
- Carlo Visco,
- Angela Amendola,
- Atto Billio,
- Roberto Marasca,
- Annalisa Chiarenza,
- Vittorio Meneghini,
- Fiorella Ilariucci,
- Monia Marchetti,
- Stefano Molica,
- Francesca Re,
- Gianluca Gaidano,
- Marcos Gonzalez,
- Francesco Forconi,
- Stefania Ciolli,
- Agostino Cortelezzi,
- Marco Montillo,
- Lukas Smolej,
- Anna Schuh,
- Toby A. Eyre,
- Ben Kennedy,
- Kris M. Bowles,
- Marco Vignetti,
- Javier de la Serna,
- Carol Moreno,
- Robin Foà,
- Paolo Ghia
Affiliations
- Antonio Cuneo
- Hematology, Department of Medical Sciences, St. Anna University Hospital, Ferrara, Italy
- George Follows
- UK CLL Forum, Cambridge University Hospitals NHS Foundation Trust, UK
- Gian Matteo Rigolin
- Hematology, Department of Medical Sciences, St. Anna University Hospital, Ferrara, Italy
- Alfonso Piciocchi
- Italian Group for Adult Hematologic Diseases (GIMEMA), Data Center and Health Outcomes Research Unit, Rome, Italy
- Alessandra Tedeschi
- Hematology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Livio Trentin
- Hematology and Clinical Immunology, Department of Medicine, University of Padua, Italy
- Angeles Medina Perez
- Hospital Costa del Sol, Marbella, Málaga, Spain
- Marta Coscia
- Hematology Unit, Città della Salute e della Scienza, University of Turin, Italy
- Luca Laurenti
- Hematology, Università Cattolica del Sacro Cuore, Policlinico A. Gemelli, Rome, Italy
- Gerardo Musuraca
- Hematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
- Lucia Farina
- Hematology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy
- Alfredo Rivas Delgado
- Department of Hematology, Hospital Clinic, Institut Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Ester Maria Orlandi
- Hematology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- Piero Galieni
- Hematology and Cellular Therapy, “Ospedale C. e G. Mazzoni”, Ascoli Piceno, Italy
- Francesca Romana Mauro
- Hematology, Department of Biomedical Sciences and Hematology, “Sapienza” University, Rome, Italy
- Carlo Visco
- Hematology, San Bortolo Hospital, Vicenza, Italy
- Angela Amendola
- Hematology, San Carlo Hospital, Potenza, Italy
- Atto Billio
- Hematology and Transplant Unit, San Maurizio Hospital, Azienda Sanitaria dell’Alto Adige, Bolzano, Italy
- Roberto Marasca
- Hematology Unit, University Hospital, Modena, Italy
- Annalisa Chiarenza
- Hematology Unit, Azienda Universitaria Ospedaliera Policlinico Vittorio Emanuele, Catania, Italy
- Vittorio Meneghini
- Hematology, Department of Cell Therapy and Hematology, University Hospital, Verona, Italy
- Fiorella Ilariucci
- Hematology Unit, Arcispedale S. Maria Nuova, Reggio Emilia, Italy
- Monia Marchetti
- Oncology Unit, Cardinal Massaia Hospital, Asti, Italy
- Stefano Molica
- Hematology Unit, A. Pugliese Hospital, Azienda Ospedaliera Pugliese Ciaccio, Catanzaro, Italy
- Francesca Re
- Hematology, University Hospital, Parma, Italy
- Gianluca Gaidano
- Hematology, DIMECS e Dipartimento Oncologico, Università del Piemonte Orientale Amedeo Avogadro, Novara, Italy
- Marcos Gonzalez
- Hematology, University Hospital-IBSAL and CIBERONC, Salamanca, Spain
- Francesco Forconi
- Haematology Department, University Hospital National Health Service Trust, Southampton, UK
- Stefania Ciolli
- Hematology Unit, Careggi Hospital, Florence, Italy
- Agostino Cortelezzi
- Hematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Italy
- Marco Montillo
- Hematology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Lukas Smolej
- Department of Hematology, University Hospital, Hradec Kralove, Czech Republic
- Anna Schuh
- UK CLL Forum, Oxford University Hospitals NHS Foundation Trust, UK
- Toby A. Eyre
- Oxford University Hospitals NHS Foundation Trust, UK
- Ben Kennedy
- University Hospitals of Leicester NHS Trust, UK
- Kris M. Bowles
- Norwich Medical School, UK
- Marco Vignetti
- Italian Group for Adult Hematologic Diseases (GIMEMA), Data Center and Health Outcomes Research Unit, Rome, Italy
- Javier de la Serna
- Hematology Unit, Hospital Universitario 12 de Octubre, Madrid, Spain
- Carol Moreno
- Hospital de la Santa Creu i Sant Pau, Barcellona, Spain
- Robin Foà
- Hematology, Department of Biomedical Sciences and Hematology, “Sapienza” University, Rome, Italy
- Paolo Ghia
- Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy
- DOI
- https://doi.org/10.3324/haematol.2018.189837
- Journal volume & issue
-
Vol. 103,
no. 7
Abstract
We performed an observational study on the efficacy of ben-damustine and rituximab (BR) as first salvage regimen in chronic lymphocytic leukemia (CLL). In an intention-to-treat analysis including 237 patients, the median progression-free survival (PFS) was 25 months. The presence of del(17p), unmutated IGHV and advanced stage were associated with a shorter PFS at multivariate analysis. The median time-to-next treatment was 31.3 months. Front-line treatment with a chemoimmunotherapy regimen was the only predictive factor for a shorter time to next treatment at multivariate analysis. The median overall survival (OS) was 74.5 months. Advanced disease stage (i.e. Rai stage III-IV or Binet stage C) and resistant disease were the only parameters significantly associated with a shorter OS. Grade 3-5 infections were recorded in 6.3% of patients. A matched-adjusted indirect comparison with ibrutinib given second-line within Named Patient Programs in the United Kingdom and in Italy was carried out with OS as objective end point. When restricting the analysis to patients with intact 17p who had received chemoimmunotherapy in first line, there was no difference in OS between patients treated with ibrutinib (63% alive at 36 months) and patients treated with BR (74.4% alive at 36 months). BR is an efficacious first salvage regimen in CLL in a real-life population, including the elderly and unfit patients. BR and ibrutinib may be equally effective in terms of OS when used as first salvage treatment in patients without 17p deletion.
