PMID- 33677466
OWN - NLM
STAT- MEDLINE
DCOM- 20220107
LR  - 20220107
IS  - 2044-5385 (Electronic)
IS  - 2044-5385 (Linking)
VI  - 11
IP  - 3
DP  - 2021 Mar 6
TI  - Long-term safety and efficacy of givinostat in polycythemia vera: 4-year mean 
      follow up of three phase 1/2 studies and a compassionate use program.
PG  - 53
LID - 10.1038/s41408-021-00445-z [doi]
LID - 53
AB  - Polycythemia vera (PV) is a BCR-ABL1-negative myeloproliferative neoplasm (MPN) 
      characterized by excessive proliferation of erythroid, myeloid, and 
      megakaryocytic components in the bone marrow, mainly due to a Janus kinase 2 gene 
      mutation (JAK2(V617F)). Givinostat, a histone-deacetylase inhibitor that 
      selectively targets JAK2(V617F) cell growth, has demonstrated good efficacy and 
      safety in three phase 1/2 studies in patients with PV. This manuscript focuses on 
      the 4-year mean (2.8 year median) follow-up of an open-label, long-term study 
      that enrolled 51 patients with PV (out of a total of 54 with MPN) who received 
      clinical benefit from givinostat in these previous studies or on compassionate 
      use, and who continued to receive givinostat at the last effective and tolerated 
      dose. The primary objectives are to determine givinostat's long-term safety and 
      tolerability, and efficacy evaluated by the investigators according to 
      internationally recognized response criteria. During follow-up, only 10% of PV 
      patients reported Grade 3 treatment-related adverse events (AEs), while none had 
      Grade 4 or 5 treatment-related AEs. The overall response rate for the duration of 
      follow-up was always greater than 80% in patients with PV. In conclusion, 
      givinostat demonstrated a good safety and efficacy profile in patients with PV, 
      data supporting long-term use in this population.
FAU - Rambaldi, Alessandro
AU  - Rambaldi A
AUID- ORCID: 0000-0002-3739-7502
AD  - Department of Oncology and Hematology University of Milan, and Azienda 
      SocioSanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy. 
      alessandro.rambaldi@unimi.it.
FAU - Iurlo, Alessandra
AU  - Iurlo A
AUID- ORCID: 0000-0002-4401-0812
AD  - Hematology Division, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 
      Milan, Italy.
FAU - Vannucchi, Alessandro M
AU  - Vannucchi AM
AUID- ORCID: 0000-0001-5755-0730
AD  - Center Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, 
      University of Florence, Florence, Italy.
FAU - Martino, Bruno
AU  - Martino B
AD  - Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli, Haematology Unit, Reggio 
      Calabria, Italy.
FAU - Guarini, Attilio
AU  - Guarini A
AD  - Hematology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy.
FAU - Ruggeri, Marco
AU  - Ruggeri M
AD  - U.O. Haematology, San Bortolo Hospital, Vicenza, Italy.
FAU - von Bubnoff, Nikolas
AU  - von Bubnoff N
AUID- ORCID: 0000-0001-9593-8947
AD  - Department of Haematology, Oncology and Stem Cell Transplantation, Medical 
      Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
AD  - Department of Haematology and Oncology, Medical Center, University of 
      Schleswig-Holstein, Campus Lubeck, Lubeck, Germany.
FAU - De Muro, Marianna
AU  - De Muro M
AD  - Hematology and Stem Cells Transplantation Unit, Campus Bio-Medico, University 
      Hospital, Rome, Italy.
FAU - McMullin, Mary Frances
AU  - McMullin MF
AUID- ORCID: 0000-0002-0773-0204
AD  - Centre for Medical Education, Queen's University Belfast, Belfast, United 
      Kingdom.
FAU - Luciani, Stefania
AU  - Luciani S
AD  - Dipartimento Oncologia-Ematologia, U.O. Complessa Ematologia Clinica, Presidio 
      Ospedaliero "Spirito Santo"- A.S.L. Azienda Sanitaria Locale, Pescara, Italy.
FAU - Martinelli, Vincenzo
AU  - Martinelli V
AD  - Dipartimento di Medicina Clinica e Chirurgia, Ematologia, Universita degli Studi 
      di Napoli Federico II, Naples, Italy.
FAU - Nogai, Axel
AU  - Nogai A
AD  - Division of Hematology and Oncology at Campus Benjamin Franklin (CBF), Charite, 
      Berlin, Germany.
FAU - Rosti, Vittorio
AU  - Rosti V
AD  - Fondazione I.R.C.C.S. Policlinico San Matteo di Pavia, Centro per lo Studio e la 
      Cura della Mielofibrosi, Laboratorio Biochimica, Biotecnologie e Diagnostica 
      Avanzata, Pavia, Italy.
FAU - Ricco, Alessandra
AU  - Ricco A
AD  - Azienda Ospedaliero-Universitaria Policlinico Consorziale di Bari, U. O. 
      Ematologia con Trapianto - Ambulatorio, Bari, Italy.
FAU - Bettica, Paolo
AU  - Bettica P
AD  - Clinical R&D Department, Italfarmaco S.p.A, Cinisello Balsamo, Italy.
FAU - Manzoni, Sara
AU  - Manzoni S
AD  - Clinical R&D Department, Italfarmaco S.p.A, Cinisello Balsamo, Italy.
FAU - Di Tollo, Silvia
AU  - Di Tollo S
AD  - Clinical R&D Department, Italfarmaco S.p.A, Cinisello Balsamo, Italy.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20210306
PL  - United States
TA  - Blood Cancer J
JT  - Blood cancer journal
JID - 101568469
RN  - 0 (Carbamates)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 5P60F84FBH (givinostat)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Carbamates/adverse effects/*therapeutic use
MH  - Female
MH  - Follow-Up Studies
MH  - Histone Deacetylase Inhibitors/adverse effects/*therapeutic use
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Polycythemia Vera/*drug therapy
MH  - Treatment Outcome
PMC - PMC7936975
COIS- A.Ra. has received honoraria for consultancy, and travel support from Italfarmaco 
      S.p.A., Gilead, Amgen, Novartis, Pfizer, Celgene, Sanofi, Astellas, and Roche. 
      A.I. has received speaker honoraria from Novartis, Pfizer, Incyte, BMS, and 
      Celgene. A.M.V. has received honoraria for advisory board participation from 
      Novartis, Celgene, Incyte, CTI, and Italfarmaco, and for lectures from Novartis, 
      and CTI. B.M. has no conflicts to disclose. A.G. has no conflicts to disclose. 
      M.R. has no conflicts to disclose. N.v.B. received research funding from 
      Novartis. M.D.M. has no conflicts to disclose. M.F.M. has received honoraria and 
      has attended advisory boards with Novartis, Astellas, and Italfarmaco, and has 
      received honoraria from Celgene. S.L. has no conflicts to disclose. V.M. has no 
      conflicts to disclose. A.N. has received travel grants from Celgene and Takeda, 
      and has attended advisory boards with Celgene, Takeda, Sanofi, Janssen, and 
      Alexion. V.R. has no conflicts to disclose. A.Ri. has received honoraria for 
      advisory board participation from Novartis, Alexion, and Sanofi. P.B., S.M., and 
      S.D.T are employees of Italfarmaco SpA, the sponsor of the study.
EDAT- 2021/03/08 06:00
MHDA- 2022/01/08 06:00
PMCR- 2021/03/06
CRDT- 2021/03/07 20:40
PHST- 2020/11/17 00:00 [received]
PHST- 2021/02/19 00:00 [accepted]
PHST- 2021/02/18 00:00 [revised]
PHST- 2021/03/07 20:40 [entrez]
PHST- 2021/03/08 06:00 [pubmed]
PHST- 2022/01/08 06:00 [medline]
PHST- 2021/03/06 00:00 [pmc-release]
AID - 10.1038/s41408-021-00445-z [pii]
AID - 445 [pii]
AID - 10.1038/s41408-021-00445-z [doi]
PST - epublish
SO  - Blood Cancer J. 2021 Mar 6;11(3):53. doi: 10.1038/s41408-021-00445-z.