Long-term outcomes of 107 patients with myelofibrosis receiving JAK1/JAK2 inhibitor ruxolitinib: Survival advantage in comparison to matched historical controls

Srdan Verstovsek, Hagop M. Kantarjian, Zeev Estrov, Jorge E. Cortes, Deborah A. Thomas, Tapan Kadia, Sherry Pierce, Elias Jabbour, Gautham Borthakur, Elisa Rumi, Ester Pungolino, Enrica Morra, Domenica Caramazza, Mario Cazzola, Francesco Passamonti

Research output: Contribution to journalArticle

Abstract

Ruxolitinib is JAK1/JAK2 inhibitor with established clinical benefit in myelofibrosis (MF). We analyzed long-term outcomes of 107 patients with intermediate-2 or high-risk MF receiving ruxolitinib at MD Anderson Cancer Center (MDACC) on phase 1/2 trial. After a median of 32 months of follow-up, 58 patients (54%) were still receiving ruxolitinib, with overall survival (OS) of 69%. The splenomegaly and symptom reductions achieved with ruxolitinib were sustained with long-term therapy. Therapy was well tolerated; discontinuation rates at 1, 2, and 3 years were 24%, 36%, and 46%, respectively. OS of 107 MDACC patients was significantly better (P = .005) than that of 310 matched (based on trial enrollment criteria) historical control patients, primarily because of highly significant difference in OS in the high-risk subgroup (P = .006). Furthermore, among MDACC patients, those with high-risk MF experienced the same OS as those with intermediate-2 risk. Patients with ≥ 50% reduction in splenomegaly had significantly prolonged survival versus those with < 25% reduction (P < .0001). Comparison of discontinuation rates and reasons for stopping the therapy to those reported for other 51 patients in the phase 1/2 trial, and 155 ruxolitinib-treated patients in phase 3 COMFORT-I study, suggest that continued therapy with ruxolitinib at optimal doses contributes to the benefits seen, including OS benefit.

Original languageEnglish (US)
Pages (from-to)1202-1209
Number of pages8
JournalBlood
Volume120
Issue number6
DOIs
StatePublished - Aug 9 2012
Externally publishedYes

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Primary Myelofibrosis
Survival
Splenomegaly
Neoplasms
INCB018424
Therapeutics

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Long-term outcomes of 107 patients with myelofibrosis receiving JAK1/JAK2 inhibitor ruxolitinib : Survival advantage in comparison to matched historical controls. / Verstovsek, Srdan; Kantarjian, Hagop M.; Estrov, Zeev; Cortes, Jorge E.; Thomas, Deborah A.; Kadia, Tapan; Pierce, Sherry; Jabbour, Elias; Borthakur, Gautham; Rumi, Elisa; Pungolino, Ester; Morra, Enrica; Caramazza, Domenica; Cazzola, Mario; Passamonti, Francesco.

In: Blood, Vol. 120, No. 6, 09.08.2012, p. 1202-1209.

Research output: Contribution to journalArticle

Verstovsek, S, Kantarjian, HM, Estrov, Z, Cortes, JE, Thomas, DA, Kadia, T, Pierce, S, Jabbour, E, Borthakur, G, Rumi, E, Pungolino, E, Morra, E, Caramazza, D, Cazzola, M & Passamonti, F 2012, 'Long-term outcomes of 107 patients with myelofibrosis receiving JAK1/JAK2 inhibitor ruxolitinib: Survival advantage in comparison to matched historical controls', Blood, vol. 120, no. 6, pp. 1202-1209. https://doi.org/10.1182/blood-2012-02-414631
Verstovsek, Srdan ; Kantarjian, Hagop M. ; Estrov, Zeev ; Cortes, Jorge E. ; Thomas, Deborah A. ; Kadia, Tapan ; Pierce, Sherry ; Jabbour, Elias ; Borthakur, Gautham ; Rumi, Elisa ; Pungolino, Ester ; Morra, Enrica ; Caramazza, Domenica ; Cazzola, Mario ; Passamonti, Francesco. / Long-term outcomes of 107 patients with myelofibrosis receiving JAK1/JAK2 inhibitor ruxolitinib : Survival advantage in comparison to matched historical controls. In: Blood. 2012 ; Vol. 120, No. 6. pp. 1202-1209.
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abstract = "Ruxolitinib is JAK1/JAK2 inhibitor with established clinical benefit in myelofibrosis (MF). We analyzed long-term outcomes of 107 patients with intermediate-2 or high-risk MF receiving ruxolitinib at MD Anderson Cancer Center (MDACC) on phase 1/2 trial. After a median of 32 months of follow-up, 58 patients (54{\%}) were still receiving ruxolitinib, with overall survival (OS) of 69{\%}. The splenomegaly and symptom reductions achieved with ruxolitinib were sustained with long-term therapy. Therapy was well tolerated; discontinuation rates at 1, 2, and 3 years were 24{\%}, 36{\%}, and 46{\%}, respectively. OS of 107 MDACC patients was significantly better (P = .005) than that of 310 matched (based on trial enrollment criteria) historical control patients, primarily because of highly significant difference in OS in the high-risk subgroup (P = .006). Furthermore, among MDACC patients, those with high-risk MF experienced the same OS as those with intermediate-2 risk. Patients with ≥ 50{\%} reduction in splenomegaly had significantly prolonged survival versus those with < 25{\%} reduction (P < .0001). Comparison of discontinuation rates and reasons for stopping the therapy to those reported for other 51 patients in the phase 1/2 trial, and 155 ruxolitinib-treated patients in phase 3 COMFORT-I study, suggest that continued therapy with ruxolitinib at optimal doses contributes to the benefits seen, including OS benefit.",
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AU - Kantarjian, Hagop M.

AU - Estrov, Zeev

AU - Cortes, Jorge E.

AU - Thomas, Deborah A.

AU - Kadia, Tapan

AU - Pierce, Sherry

AU - Jabbour, Elias

AU - Borthakur, Gautham

AU - Rumi, Elisa

AU - Pungolino, Ester

AU - Morra, Enrica

AU - Caramazza, Domenica

AU - Cazzola, Mario

AU - Passamonti, Francesco

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N2 - Ruxolitinib is JAK1/JAK2 inhibitor with established clinical benefit in myelofibrosis (MF). We analyzed long-term outcomes of 107 patients with intermediate-2 or high-risk MF receiving ruxolitinib at MD Anderson Cancer Center (MDACC) on phase 1/2 trial. After a median of 32 months of follow-up, 58 patients (54%) were still receiving ruxolitinib, with overall survival (OS) of 69%. The splenomegaly and symptom reductions achieved with ruxolitinib were sustained with long-term therapy. Therapy was well tolerated; discontinuation rates at 1, 2, and 3 years were 24%, 36%, and 46%, respectively. OS of 107 MDACC patients was significantly better (P = .005) than that of 310 matched (based on trial enrollment criteria) historical control patients, primarily because of highly significant difference in OS in the high-risk subgroup (P = .006). Furthermore, among MDACC patients, those with high-risk MF experienced the same OS as those with intermediate-2 risk. Patients with ≥ 50% reduction in splenomegaly had significantly prolonged survival versus those with < 25% reduction (P < .0001). Comparison of discontinuation rates and reasons for stopping the therapy to those reported for other 51 patients in the phase 1/2 trial, and 155 ruxolitinib-treated patients in phase 3 COMFORT-I study, suggest that continued therapy with ruxolitinib at optimal doses contributes to the benefits seen, including OS benefit.

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