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

被引:13
作者
Zaja, Francesco [1 ,2 ]
Salvi, Flavia [3 ]
Rossi, Maura [4 ]
Sabattini, Elena [5 ]
Evangelista, Andrea [5 ]
Ciccone, Giovannino [6 ,7 ]
Angelucci, Emanuele [8 ]
Gaidano, Gianluca [9 ]
Zanni, Manuela [9 ]
Ladetto, Marco [3 ]
Chiappella, Annalisa [10 ]
Vitolo, Umberto [10 ]
Zinzani, Pier Luigi [11 ]
Califano, Catello [12 ]
Tucci, Alessandra [13 ,14 ]
Patti, Caterina [15 ]
Pileri, Stefano A. [16 ]
Lenti, Valentina [17 ]
Piccaluga, Pier Paolo [4 ]
Cavallo, Federica [18 ]
Volpetti, Stefano [19 ,20 ]
Perali, Giulia [19 ,20 ]
Assouline, Sarit [21 ]
Mann, Koren Kathleen [22 ]
Morin, Ryan [23 ]
Alcaide, Miguel [23 ]
Bushell, Kevin [23 ]
Fanin, Renato [1 ,2 ]
Levis, Alessandro [17 ]
机构
[1] Univ Udine, Clin Ematol, DAME, Udine, Italy
[2] Univ Udine, Unita Terapie Cellulari Carlo Melzi, DAME, Udine, Italy
[3] AO SS Antonio & Biagio & C Arrigo, SC Ematol, Alessandria, Italy
[4] Univ Hosp Bologna, Unit Haemolymphopathol, Dept Expt Diagnost & Specialty Med, Bologna, Italy
[5] Univ Hosp Bologna, Dept Hematol & Oncol, Unit Haemolymphopathol, Bologna, Italy
[6] AOU Citta Salute & Sci Torino, Unit Clin Epidemiol, Turin, Italy
[7] CPO Piemonte, Turin, Italy
[8] IRCCS AOU San Martino IST, UOC Ematol, Genoa, Italy
[9] Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Hematol, Novara, Italy
[10] AOU Citta Salute & Sci, SC Ematol, Turin, Italy
[11] Univ Bologna, Inst Hematol L&A Seragnoli, Bologna, Italy
[12] Osped Umberto I, UO Med Oncoematol, Nocera Inferiore, Italy
[13] Spedali Civil Brescia, SC Ematol, Brescia, Italy
[14] Spedali Civil Brescia, Dipartimento Oncol Med, Brescia, Italy
[15] Osped V Cervello, UOC Ematol, Palermo, Italy
[16] Milano Univ, Sch Med, European Inst Oncol, Haematopathol Unit, Bologna, Italy
[17] Fdn Italiana Linfomi, Alessandria, Italy
[18] Univ Torino, Azienda Osped Univ Citta Salute & Sci, Turin, Italy
[19] Azienda Sanit Univ Integrata, Clin Ematol, Udine, Italy
[20] Azienda Sanit Univ Integrata, Unita Terapie Cellulari Carlo Melzi, Udine, Italy
[21] McGill Univ, Jewish Gen Hosp, Div Hematol, Montreal, PQ, Canada
[22] McGill Univ, Lady Davis Inst, Jewish Gen Hosp, Montreal, PQ, Canada
[23] Simon Fraser Univ, Dept Mol Biol & Biochem, Sch Comp Sci, Vancouver, BC, Canada
关键词
Diffuse large B-cell lymphoma; panobinostat; relapsed/refractory; genomic; DEACETYLASE INHIBITOR PANOBINOSTAT; HISTONE DEACETYLASES; RITUXIMAB; DISEASE; MULTICENTER; ROMIDEPSIN; MUTATION; LBH589; TRIAL; CHOP;
D O I
10.1080/10428194.2018.1452208
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:2904 / 2910
页数:7
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