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

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

doi:10.1038/s41408-021-00445-z

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

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

^*Corresponding author for this work

39 Citations (Scopus)

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 (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.

Original language	English
Article number	53
Journal	Blood Cancer Journal
Volume	11
Issue number	3
Pages (from-to)	53
DOIs	https://doi.org/10.1038/s41408-021-00445-z
Publication status	Published - 06.03.2021

Funding

This study was sponsored by Italfarmaco S.p.A. The authors would like to thank the investigators who recruited patients, and the patients at the investigative sites for their support of this study. The authors would also like to thank Tim Demuth, Aurelio Scotti, Erminio Bonizzoni, and Carlo Bianchini, all previous employees of Italfarmaco S.p.A., for their help with the development of the study protocol. David Young of Young Medical Communications and Consulting Ltd, a medical writer supported by funding from Italfarmaco S.p.A., provided drafts and editorial assistance to the authors during preparation of this manuscript. 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.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Research Area: Luebeck Integrated Oncology Network (LION)

DFG Research Classification Scheme

2.22-14 Hematology, Oncology

Access to Document

10.1038/s41408-021-00445-z

Cite this

Rambaldi, A., Iurlo, A., Vannucchi, A. M., Martino, B., Guarini, A., Ruggeri, M., von Bubnoff, N., De Muro, M., McMullin, M. F., Luciani, S., Martinelli, V., Nogai, A., Rosti, V., Ricco, A., Bettica, P., Manzoni, S., & Di Tollo, S. (2021). 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. Blood Cancer Journal, 11(3), 53. Article 53. https://doi.org/10.1038/s41408-021-00445-z

@article{c4650279cd0548328d5d05c1546b07de,

title = "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{\textquoteright}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.",

author = "Alessandro Rambaldi and Alessandra Iurlo and Vannucchi, \{Alessandro M.\} and Bruno Martino and Attilio Guarini and Marco Ruggeri and \{von Bubnoff\}, Nikolas and \{De Muro\}, Marianna and McMullin, \{Mary Frances\} and Stefania Luciani and Vincenzo Martinelli and Axel Nogai and Vittorio Rosti and Alessandra Ricco and Paolo Bettica and Sara Manzoni and \{Di Tollo\}, Silvia",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = mar,

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doi = "10.1038/s41408-021-00445-z",

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Rambaldi, A, Iurlo, A, Vannucchi, AM, Martino, B, Guarini, A, Ruggeri, M, von Bubnoff, N, De Muro, M, McMullin, MF, Luciani, S, Martinelli, V, Nogai, A, Rosti, V, Ricco, A, Bettica, P, Manzoni, S & Di Tollo, S 2021, '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', Blood Cancer Journal, vol. 11, no. 3, 53, pp. 53. https://doi.org/10.1038/s41408-021-00445-z

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. / Rambaldi, Alessandro; Iurlo, Alessandra; Vannucchi, Alessandro M. et al.
In: Blood Cancer Journal, Vol. 11, No. 3, 53, 06.03.2021, p. 53.

Research output: Journal Articles › Journal articles › Research › peer-review

TY - JOUR

T1 - 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

AU - Rambaldi, Alessandro

AU - Iurlo, Alessandra

AU - Vannucchi, Alessandro M.

AU - Martino, Bruno

AU - Guarini, Attilio

AU - Ruggeri, Marco

AU - von Bubnoff, Nikolas

AU - De Muro, Marianna

AU - McMullin, Mary Frances

AU - Luciani, Stefania

AU - Martinelli, Vincenzo

AU - Nogai, Axel

AU - Rosti, Vittorio

AU - Ricco, Alessandra

AU - Bettica, Paolo

AU - Manzoni, Sara

AU - Di Tollo, Silvia

PY - 2021/3/6

Y1 - 2021/3/6

N2 - 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.

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 (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.

UR - https://www.scopus.com/pages/publications/85102046458

UR - https://www.mendeley.com/catalogue/eeab777a-b316-327c-a039-a677fa20b6d8/

U2 - 10.1038/s41408-021-00445-z

DO - 10.1038/s41408-021-00445-z

M3 - Journal articles

C2 - 33677466

AN - SCOPUS:85102046458

SN - 2044-5385

VL - 11

SP - 53

JO - Blood Cancer Journal

JF - Blood Cancer Journal

IS - 3

M1 - 53

ER -

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

Funding

UN SDGs

Research Areas and Centers

DFG Research Classification Scheme

Access to Document

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