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.

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.

• Authors: Alessandro Rambaldi, Alessandra Iurlo, Alessandro M Vannucchi, Bruno Martino, Attilio Guarini, Marco Ruggeri, Nikolas von Bubnoff, Marianna De Muro, Mary Frances McMullin, Stefania Luciani, Vincenzo Martinelli, Axel Nogai, Vittorio Rosti, Alessandra Ricco, Paolo Bettica, Sara Manzoni, Silvia Di Tollo
• Journal: Blood cancer journal (Blood Cancer J) Vol. 11 Issue 3 Pg. 53 (03 06 2021) ISSN: 2044-5385 [Electronic] United States
• PMID: 33677466 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Carbamates
• Histone Deacetylase Inhibitors
• givinostat

Topics

• Adult
• Aged
• Carbamates (adverse effects, therapeutic use)
• Female
• Follow-Up Studies
• Histone Deacetylase Inhibitors (adverse effects, therapeutic use)
• Humans
• Male
• Middle Aged
• Polycythemia Vera (drug therapy)
• Treatment Outcome