Ruxolitinib discontinuation in polycythemia vera: Patient characteristics, outcomes, and salvage strategies from a large multi-institutional database

Douglas Tremblay; Lukas Ronner; Nikolai Podoltsev; Jason Gotlib; Mark Heaney; Andrew Kuykendall; Casey O'Connell; Jamile M. Shammo; Angela Fleischman; Ruben Mesa; Abdulraheem Yacoub; Ronald Hoffman; Erin Moshier; Nicole Zubizarreta; John Mascarenhas

doi:10.1016/j.leukres.2021.106629

Ruxolitinib discontinuation in polycythemia vera: Patient characteristics, outcomes, and salvage strategies from a large multi-institutional database

Douglas Tremblay, Lukas Ronner, Nikolai Podoltsev, Jason Gotlib, Mark Heaney, Andrew Kuykendall, Casey O'Connell, Jamile M. Shammo, Angela Fleischman, Ruben Mesa, Abdulraheem Yacoub, Ronald Hoffman, Erin Moshier, Nicole Zubizarreta, John Mascarenhas^*

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Ruxolitinib is approved for the treatment of patients with polycythemia vera (PV) who are intolerant or resistant to hydroxyurea. While ruxolitinib discontinuation in myelofibrosis is associated with dismal outcomes, the analogous experience in PV has not been reported. Using a large, multi-institutional database of PV patients, we identified 93 patients with PV who were treated with ruxolitinib, of whom 22 discontinued therapy. Adverse events were the primary reason for discontinuation. After a median follow-up of 18.2 months following ruxolitinib discontinuation, no patients experienced a thrombotic event. One patient died 20.8 months after discontinuation. As compared with the 71 patients who were still receiving treatment with ruxolitinib at last follow up, patients who discontinued ruxolitinib were older at time of treatment initiation (67.5 versus 64.8 years, p = 0.0058), but had similar patient and disease characteristics. After discontinuation, only 4 patients (18 %) received subsequent cytoreductive therapy, including hydroxyurea in one patient and pegylated interferon α-2a in three patients. In stark contrast to the experience in myelofibrosis, discontinuation of ruxolitinib in PV was associated with generally favorable outcomes. However, there is a lack of available salvage therapies, highlighting the need for further therapeutic development in PV.

Original language	English (US)
Article number	106629
Journal	Leukemia Research
Volume	109
DOIs	https://doi.org/10.1016/j.leukres.2021.106629
State	Published - Oct 2021

Funding

This work was supported by an unrestricted educational grant from PharmaEssentia. PharmaEssentia did not participate in the conception of the project, acquisition of data, analysis of the data, or writing of the manuscript.NP has served on the advisory board and received honoraria from Incyte and PharmaEssentia; JG has received research funding, honoraria, and served on the advisory board for Incyte, Kartos, and Protagonist Therapeutics; MH has received research funding/consulted for Novartis, Blue Medicines, PharmaEssentia; AK has served on the advisory board and received honoraria from Protagonist Therapeutics, PharmaEssentia, and Incyte; JMS has received research funding from AbbVie, Bristol Myers Squibb, CTI Biopharma, Kartos, and Incyte and has received honoraria from Incyte, Bristol Myers Squibb, and Novartis and serves on the speakers bureau for Incyte and Bristol Myers Squibb; AF is on the speakers bureau for Incyte, Bristol Myers Squibb, and PharmaEssentia; RM has received research funding from Incyte, Gilead, CTI Biopharma, Celgene, AbbVie, and Genentech and has received honoraria from Novartis, Seirra Oncology, La Jolla Pharma and AOP Orphan; AY is on the speakers bureau for Incyte; RH is consultant for Protagonist and serves on Data Safety Monitoring Boards for Novartis and AbbVie; JM received consulting fees from Incyte, Roche, Geron, Constellation, PharmaEssentia, BMS, Celgene and Kartos and received contracted research funding paid to his institution from CTI Biopharma, Incyte, Roche, Merck, Forbius, Promedior, Novartis, Janssen and Kartos. DT, LR, CO, EM, and NZ have no conflict of interest to report.

Keywords

Discontinuation
Intolerance
Polycythemia vera
Ruxolitinib

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

UN SDGs

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

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10.1016/j.leukres.2021.106629

Cite this

Tremblay, D., Ronner, L., Podoltsev, N., Gotlib, J., Heaney, M., Kuykendall, A., O'Connell, C., Shammo, J. M., Fleischman, A., Mesa, R., Yacoub, A., Hoffman, R., Moshier, E., Zubizarreta, N., & Mascarenhas, J. (2021). Ruxolitinib discontinuation in polycythemia vera: Patient characteristics, outcomes, and salvage strategies from a large multi-institutional database. Leukemia Research, 109, Article 106629. https://doi.org/10.1016/j.leukres.2021.106629

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title = "Ruxolitinib discontinuation in polycythemia vera: Patient characteristics, outcomes, and salvage strategies from a large multi-institutional database",

abstract = "Ruxolitinib is approved for the treatment of patients with polycythemia vera (PV) who are intolerant or resistant to hydroxyurea. While ruxolitinib discontinuation in myelofibrosis is associated with dismal outcomes, the analogous experience in PV has not been reported. Using a large, multi-institutional database of PV patients, we identified 93 patients with PV who were treated with ruxolitinib, of whom 22 discontinued therapy. Adverse events were the primary reason for discontinuation. After a median follow-up of 18.2 months following ruxolitinib discontinuation, no patients experienced a thrombotic event. One patient died 20.8 months after discontinuation. As compared with the 71 patients who were still receiving treatment with ruxolitinib at last follow up, patients who discontinued ruxolitinib were older at time of treatment initiation (67.5 versus 64.8 years, p = 0.0058), but had similar patient and disease characteristics. After discontinuation, only 4 patients (18 %) received subsequent cytoreductive therapy, including hydroxyurea in one patient and pegylated interferon α-2a in three patients. In stark contrast to the experience in myelofibrosis, discontinuation of ruxolitinib in PV was associated with generally favorable outcomes. However, there is a lack of available salvage therapies, highlighting the need for further therapeutic development in PV.",

keywords = "Discontinuation, Intolerance, Polycythemia vera, Ruxolitinib",

author = "Douglas Tremblay and Lukas Ronner and Nikolai Podoltsev and Jason Gotlib and Mark Heaney and Andrew Kuykendall and Casey O'Connell and Shammo, {Jamile M.} and Angela Fleischman and Ruben Mesa and Abdulraheem Yacoub and Ronald Hoffman and Erin Moshier and Nicole Zubizarreta and John Mascarenhas",

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Tremblay, D, Ronner, L, Podoltsev, N, Gotlib, J, Heaney, M, Kuykendall, A, O'Connell, C, Shammo, JM, Fleischman, A, Mesa, R, Yacoub, A, Hoffman, R, Moshier, E, Zubizarreta, N & Mascarenhas, J 2021, 'Ruxolitinib discontinuation in polycythemia vera: Patient characteristics, outcomes, and salvage strategies from a large multi-institutional database', Leukemia Research, vol. 109, 106629. https://doi.org/10.1016/j.leukres.2021.106629

TY - JOUR

T1 - Ruxolitinib discontinuation in polycythemia vera

T2 - Patient characteristics, outcomes, and salvage strategies from a large multi-institutional database

AU - Tremblay, Douglas

AU - Ronner, Lukas

AU - Podoltsev, Nikolai

AU - Gotlib, Jason

AU - Heaney, Mark

AU - Kuykendall, Andrew

AU - O'Connell, Casey

AU - Shammo, Jamile M.

AU - Fleischman, Angela

AU - Mesa, Ruben

AU - Yacoub, Abdulraheem

AU - Hoffman, Ronald

AU - Moshier, Erin

AU - Zubizarreta, Nicole

AU - Mascarenhas, John

PY - 2021/10

Y1 - 2021/10

N2 - Ruxolitinib is approved for the treatment of patients with polycythemia vera (PV) who are intolerant or resistant to hydroxyurea. While ruxolitinib discontinuation in myelofibrosis is associated with dismal outcomes, the analogous experience in PV has not been reported. Using a large, multi-institutional database of PV patients, we identified 93 patients with PV who were treated with ruxolitinib, of whom 22 discontinued therapy. Adverse events were the primary reason for discontinuation. After a median follow-up of 18.2 months following ruxolitinib discontinuation, no patients experienced a thrombotic event. One patient died 20.8 months after discontinuation. As compared with the 71 patients who were still receiving treatment with ruxolitinib at last follow up, patients who discontinued ruxolitinib were older at time of treatment initiation (67.5 versus 64.8 years, p = 0.0058), but had similar patient and disease characteristics. After discontinuation, only 4 patients (18 %) received subsequent cytoreductive therapy, including hydroxyurea in one patient and pegylated interferon α-2a in three patients. In stark contrast to the experience in myelofibrosis, discontinuation of ruxolitinib in PV was associated with generally favorable outcomes. However, there is a lack of available salvage therapies, highlighting the need for further therapeutic development in PV.

AB - Ruxolitinib is approved for the treatment of patients with polycythemia vera (PV) who are intolerant or resistant to hydroxyurea. While ruxolitinib discontinuation in myelofibrosis is associated with dismal outcomes, the analogous experience in PV has not been reported. Using a large, multi-institutional database of PV patients, we identified 93 patients with PV who were treated with ruxolitinib, of whom 22 discontinued therapy. Adverse events were the primary reason for discontinuation. After a median follow-up of 18.2 months following ruxolitinib discontinuation, no patients experienced a thrombotic event. One patient died 20.8 months after discontinuation. As compared with the 71 patients who were still receiving treatment with ruxolitinib at last follow up, patients who discontinued ruxolitinib were older at time of treatment initiation (67.5 versus 64.8 years, p = 0.0058), but had similar patient and disease characteristics. After discontinuation, only 4 patients (18 %) received subsequent cytoreductive therapy, including hydroxyurea in one patient and pegylated interferon α-2a in three patients. In stark contrast to the experience in myelofibrosis, discontinuation of ruxolitinib in PV was associated with generally favorable outcomes. However, there is a lack of available salvage therapies, highlighting the need for further therapeutic development in PV.

KW - Discontinuation

KW - Intolerance

KW - Polycythemia vera

KW - Ruxolitinib

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Ruxolitinib discontinuation in polycythemia vera: Patient characteristics, outcomes, and salvage strategies from a large multi-institutional database

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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