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Leukemia & Lymphoma Volume 59, 2018 - Issue 12
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Original Article: Clinical

Single-agent panobinostat for relapsed/refractory diffuse large B-cell lymphoma: clinical outcome and correlation with genomic data. A phase 2 study of the Fondazione Italiana Linfomi

Francesco ZajaClinica Ematologica ed Unità di Terapie Cellulari ‘Carlo Melzi’, DAME, University of Udine, Udine, Italy; Correspondence[email protected]
,
Flavia SalviS.C. Ematologia, A.O. SS. Antonio e Biagio e C. Arrigo, Alessandria, Italy;
,
Maura RossiUnit of Haemolymphopathology, Department of Experimental, Diagnostic and Specialty Medicine, University Hospital of Bologna, Bologna, Italy;
,
Elena SabattiniUnit of Haemolymphopathology, Department of Hematology and Oncology, University Hospital of Bologna, Bologna, Italy;
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Andrea EvangelistaUnit of Haemolymphopathology, Department of Hematology and Oncology, University Hospital of Bologna, Bologna, Italy;
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Giovannino CicconeUnit of Clinical Epidemiology, AOU Città della Salute e della Scienza di Torino and CPO Piemonte, Torino, Italy;
,
Emanuele AngelucciU.O.C. Ematologia, IRCCS A.O.U. San Martino-IST, Genova, Italy; ORCID Iconhttp://orcid.org/0000-0002-6512-6080
ORCID Icon,
Gianluca GaidanoDivision of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy;
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Manuela ZanniDivision of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy;
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Marco LadettoS.C. Ematologia, A.O. SS. Antonio e Biagio e C. Arrigo, Alessandria, Italy;
,
Annalisa ChiappellaS.C. Ematologia, A.O.U. Città della Salute e della Scienza, Torino, Italy;
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Umberto VitoloS.C. Ematologia, A.O.U. Città della Salute e della Scienza, Torino, Italy;
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Pier Luigi ZinzaniInstitute of Hematology “L. e A. Seràgnoli”, University of Bologna, Bologna, Italy;
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Catello CalifanoU.O. Medicina-Oncoematologia, Ospedale Umberto I, Nocera Inferiore, Italy;
,
Alessandra TucciS.C. Ematologia e Dipartimento Oncologia Medica Spedali Civili, Brescia, Italy;
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Caterina PattiU.O.C. di Ematologia, Ospedale V. Cervello, Palermo, Italy;
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Stefano A. PileriHaematopathology Unit, European Institute of Oncology, Milano/University School of Medicine, Bologna, Italy;
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Valentina LentiFondazione Italiana Linfomi, Alessandria, Italy;
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Pier Paolo PiccalugaUnit of Haemolymphopathology, Department of Experimental, Diagnostic and Specialty Medicine, University Hospital of Bologna, Bologna, Italy;
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Federica CavalloUniversity of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy;
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Stefano VolpettiClinica Ematologica ed Unità di Terapie Cellulari ‘Carlo Melzi’, Azienda Sanitaria Universitaria Integrata, Udine, Italy;
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Giulia PeraliClinica Ematologica ed Unità di Terapie Cellulari ‘Carlo Melzi’, Azienda Sanitaria Universitaria Integrata, Udine, Italy;
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Sarit AssoulineDivision of Hematology, Jewish General Hospital, McGill University, Montreal, QC, Canada;
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Koren Kathleen MannLady Davis Institute, Jewish General Hospital, McGill University, Montreal, QC, Canada;
,
Ryan MorinDepartment of Molecular Biology and Biochemistry, School of Computing Science, Simon Fraser University, Vancouver, BC, Canada
,
Miguel AlcaideDepartment of Molecular Biology and Biochemistry, School of Computing Science, Simon Fraser University, Vancouver, BC, Canada
,
Kevin BushellDepartment of Molecular Biology and Biochemistry, School of Computing Science, Simon Fraser University, Vancouver, BC, Canada
,
Renato FaninClinica Ematologica ed Unità di Terapie Cellulari ‘Carlo Melzi’, DAME, University of Udine, Udine, Italy;
&
Alessandro LevisFondazione Italiana Linfomi, Alessandria, Italy;
show all
Pages 2904-2910 | Received 06 Dec 2017, Accepted 25 Feb 2018, Published online: 04 Apr 2018
 
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Abstract

We investigated panobinostat 40 mg three times weekly in 35 adult patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Overall response rate and complete response were 17.1% and 11.4%, respectively. Median progression-free survival (PFS) and overall survival were 2.4 and 7.6 months, respectively. Calculated 12, 24 and 36 months PFS were 26%, 11% and 11%, respectively. Four patients who achieved a sustained CR, continued receiving panobinostat for an overall period of 44, 48, 50, 62 months. Thrombocytopenia grade 3 (5 patients) and 4 (24 patients) represented the main toxic effect, causing dose reduction or treatment suspension in 19 patients. Genomic analysis was unable to identify any relationship between mutations and response; TP53 mutation appeared not to impact the clinical outcome. Overall, panobinostat has a modest activity in R/R DLBCL patients, however it can induce very long lasting responses in some cases. Thrombocytopenia frequently limits the use of this agent.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080\10428194.2018.1452208.

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