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 (JAK2V617F). Givinostat, a histone-deacetylase inhibitor that selectively targets JAK2V617F 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.

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 / A. Rambaldi, A. Iurlo, A.M. Vannucchi, B. Martino, A. Guarini, M. Ruggeri, N. von Bubnoff, M. De Muro, M.F. McMullin, S. Luciani, V. Martinelli, A. Nogai, V. Rosti, A. Ricco, P. Bettica, S. Manzoni, S. Di Tollo. - In: BLOOD CANCER JOURNAL. - ISSN 2044-5385. - 11:3(2021), pp. 53.1-53.7.

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

A. Rambaldi
Primo
;
2021

Abstract

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 (JAK2V617F). Givinostat, a histone-deacetylase inhibitor that selectively targets JAK2V617F 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.
Settore MED/15 - Malattie del Sangue
Article (author)
File in questo prodotto:
File Dimensione Formato  
s41408-021-00445-z.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 505.18 kB
Formato Adobe PDF
505.18 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/846820
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 7
social impact