Decreased survival and increased rate of fibrotic progression in essential thrombocythemia chronicled after the FDA approval date of anagrelide

Ayalew Tefferi, Natasha Szuber, Rangit R. Vallapureddy, Kebede Begna, Mrinal M Patnaik, Michelle A. Elliott, C. Christopher Hook, Alexandra P. Wolanskyj, Curtis A. Hanson, Rhett P. Ketterling, Animesh D Pardanani, Naseema Gangat

Research output: Contribution to journalArticle

Abstract

First-line cytoreductive drug of choice in high risk essential thrombocythemia (ET) is currently hydroxyurea, a practice based on the results of a randomized study; second-line drugs of choice include pegylated interferon-α, busulfan and anagrelide. Anagrelide clinical trials were pioneered by the late Murray N. Silverstein (1928-1998) of the Mayo Clinic whose studies led to FDA approval in March 1997. The current study represents a retrospective examination of the potential impact of anagrelide therapy on survival and disease complications in ET. 1076 patients with ET were considered (median age 58 years; females 63%); risk distribution, according to the international prognostic score for ET (IPSET), was 28% high, 42% intermediate, and 30% low. Overall (OS), myelofibrosis-free (MFFS) and thrombosis-free survival data were compared for ET patients diagnosed before and after the 1997 FDA approval date for anagrelide; a significant difference was apparent in OS (P =.006; HR 1.4, 95% CI 1.1-1.7) and MFFS (P <.001; HR 4.2, 95% CI 2.7-6.5), in favor of patients diagnosed prior to 1997; the difference was sustained during multivariable analysis that included IPSET. Similarly stratified survival data in polycythemia vera (n = 665) and primary myelofibrosis (n = 1282) showed no similar impact on survival (P =.3 and.17, respectively). The current study represents a retrospective analysis and suggests significantly decreased OS and MFFS in ET patients diagnosed after the FDA approval date of anagrelide. Whether or not anagrelide therapy was to blame for the worsening of OS and MFFS over time cannot be assumed and requires validation in a prospective study.

Original languageEnglish (US)
JournalAmerican Journal of Hematology
DOIs
StateAccepted/In press - Jan 1 2018

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Essential Thrombocythemia
Survival Rate
Primary Myelofibrosis
Survival
Busulfan
Polycythemia Vera
Hydroxyurea
Pharmaceutical Preparations
Interferons
anagrelide
Thrombosis
Clinical Trials
Prospective Studies
Therapeutics

ASJC Scopus subject areas

  • Hematology

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Decreased survival and increased rate of fibrotic progression in essential thrombocythemia chronicled after the FDA approval date of anagrelide. / Tefferi, Ayalew; Szuber, Natasha; Vallapureddy, Rangit R.; Begna, Kebede; Patnaik, Mrinal M; Elliott, Michelle A.; Christopher Hook, C.; Wolanskyj, Alexandra P.; Hanson, Curtis A.; Ketterling, Rhett P.; Pardanani, Animesh D; Gangat, Naseema.

In: American Journal of Hematology, 01.01.2018.

Research output: Contribution to journalArticle

Tefferi, Ayalew ; Szuber, Natasha ; Vallapureddy, Rangit R. ; Begna, Kebede ; Patnaik, Mrinal M ; Elliott, Michelle A. ; Christopher Hook, C. ; Wolanskyj, Alexandra P. ; Hanson, Curtis A. ; Ketterling, Rhett P. ; Pardanani, Animesh D ; Gangat, Naseema. / Decreased survival and increased rate of fibrotic progression in essential thrombocythemia chronicled after the FDA approval date of anagrelide. In: American Journal of Hematology. 2018.
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abstract = "First-line cytoreductive drug of choice in high risk essential thrombocythemia (ET) is currently hydroxyurea, a practice based on the results of a randomized study; second-line drugs of choice include pegylated interferon-α, busulfan and anagrelide. Anagrelide clinical trials were pioneered by the late Murray N. Silverstein (1928-1998) of the Mayo Clinic whose studies led to FDA approval in March 1997. The current study represents a retrospective examination of the potential impact of anagrelide therapy on survival and disease complications in ET. 1076 patients with ET were considered (median age 58 years; females 63{\%}); risk distribution, according to the international prognostic score for ET (IPSET), was 28{\%} high, 42{\%} intermediate, and 30{\%} low. Overall (OS), myelofibrosis-free (MFFS) and thrombosis-free survival data were compared for ET patients diagnosed before and after the 1997 FDA approval date for anagrelide; a significant difference was apparent in OS (P =.006; HR 1.4, 95{\%} CI 1.1-1.7) and MFFS (P <.001; HR 4.2, 95{\%} CI 2.7-6.5), in favor of patients diagnosed prior to 1997; the difference was sustained during multivariable analysis that included IPSET. Similarly stratified survival data in polycythemia vera (n = 665) and primary myelofibrosis (n = 1282) showed no similar impact on survival (P =.3 and.17, respectively). The current study represents a retrospective analysis and suggests significantly decreased OS and MFFS in ET patients diagnosed after the FDA approval date of anagrelide. Whether or not anagrelide therapy was to blame for the worsening of OS and MFFS over time cannot be assumed and requires validation in a prospective study.",
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AU - Begna, Kebede

AU - Patnaik, Mrinal M

AU - Elliott, Michelle A.

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AU - Wolanskyj, Alexandra P.

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AU - Pardanani, Animesh D

AU - Gangat, Naseema

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