Long-Term survival in patients treated with ruxolitinib for myelofibrosis: COMFORT-I and-II pooled analyses

Srdan Verstovsek, Jason Gotlib, Ruben A. Mesa, Alessandro M. Vannucchi, Jean Jacques Kiladjian, Francisco Cervantes, Claire N. Harrison, Ronald Paquette, William Sun, Ahmad Naim, Peter Langmuir, Tuochuan Dong, Prashanth Gopalakrishna, Vikas Gupta

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Background: Myelofibrosis (MF) is associated with a variety of burdensome symptoms and reduced survival compared with age-/sex-matched controls. This analysis evaluated the long-Term survival benefit with ruxolitinib, a Janus kinase (JAK)1/JAK2 inhibitor, in patients with intermediate-2 (int-2) or high-risk MF. Methods: This was an exploratory analysis of 5-year data pooled from the phase 3 COMFORT-I and-II trials. In both trials, patients could cross over to ruxolitinib from the control group (COMFORT-I, placebo; COMFORT-II, best available therapy). All continuing patients in the control groups crossed over to ruxolitinib by the 3-year follow-up. Overall survival (OS; a secondary endpoint in both trials) was evaluated using pooled intent-To-Treat data from patients randomized to ruxolitinib or the control groups. OS was also evaluated in subgroups stratified by baseline anemia and transfusion status at week 24. Results: A total of 528 patients were included in this analysis; 301 were originally randomized to ruxolitinib (COMFORT-I, n = 155; COMFORT-II, n = 146) and 227 to control (n = 154 and n = 73, respectively). The risk of death was reduced by 30% among patients randomized to ruxolitinib compared with patients in the control group (median OS, 5.3 vs 3.8 years, respectively; hazard ratio [HR], 0.70 [95% CI, 0.54-0.91]; P = 0.0065). After correcting for crossover using a rank-preserving structural failure time (RPSFT) method, the OS advantage was more pronounced for patients who were originally randomized to ruxolitinib compared with patients who crossed over from control to ruxolitinib (median OS, 5.3 vs 2.3 years; HR [ruxolitinib vs RPSFT], 0.35 [95% CI, 0.23-0.59]). An analysis of OS censoring patients at the time of crossover also demonstrated that ruxolitinib prolonged OS compared with control (median OS, 5.3 vs 2.4 years; HR [ruxolitinib vs censored at crossover], 0.53 [95% CI, 0.36-0.78]; P = 0.0013). The survival benefit with ruxolitinib was observed irrespective of baseline anemia status or transfusion requirements at week 24. Conclusions: These findings support ruxolitinib treatment for patients with int-2 or high-risk MF, regardless of anemia or transfusion status. Further analyses will be important for exploring ruxolitinib earlier in the disease course to assess the effect on the natural history of MF. Trial registration: ClinicalTrials.gov identifiers, NCT00952289 and NCT00934544.

Original languageEnglish (US)
Article number527
JournalJournal of Hematology and Oncology
Volume10
Issue number1
DOIs
StatePublished - Sep 29 2017
Externally publishedYes

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Primary Myelofibrosis
Survival
Anemia
Control Groups
INCB018424
Janus Kinase 1

Keywords

  • Anemia
  • Myelofibrosis
  • Overall survival
  • Ruxolitinib
  • Transfusion

ASJC Scopus subject areas

  • Hematology
  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

Verstovsek, S., Gotlib, J., Mesa, R. A., Vannucchi, A. M., Kiladjian, J. J., Cervantes, F., ... Gupta, V. (2017). Long-Term survival in patients treated with ruxolitinib for myelofibrosis: COMFORT-I and-II pooled analyses. Journal of Hematology and Oncology, 10(1), [527]. https://doi.org/10.1186/s13045-017-0527-7

Long-Term survival in patients treated with ruxolitinib for myelofibrosis : COMFORT-I and-II pooled analyses. / Verstovsek, Srdan; Gotlib, Jason; Mesa, Ruben A.; Vannucchi, Alessandro M.; Kiladjian, Jean Jacques; Cervantes, Francisco; Harrison, Claire N.; Paquette, Ronald; Sun, William; Naim, Ahmad; Langmuir, Peter; Dong, Tuochuan; Gopalakrishna, Prashanth; Gupta, Vikas.

In: Journal of Hematology and Oncology, Vol. 10, No. 1, 527, 29.09.2017.

Research output: Contribution to journalArticle

Verstovsek, S, Gotlib, J, Mesa, RA, Vannucchi, AM, Kiladjian, JJ, Cervantes, F, Harrison, CN, Paquette, R, Sun, W, Naim, A, Langmuir, P, Dong, T, Gopalakrishna, P & Gupta, V 2017, 'Long-Term survival in patients treated with ruxolitinib for myelofibrosis: COMFORT-I and-II pooled analyses', Journal of Hematology and Oncology, vol. 10, no. 1, 527. https://doi.org/10.1186/s13045-017-0527-7
Verstovsek, Srdan ; Gotlib, Jason ; Mesa, Ruben A. ; Vannucchi, Alessandro M. ; Kiladjian, Jean Jacques ; Cervantes, Francisco ; Harrison, Claire N. ; Paquette, Ronald ; Sun, William ; Naim, Ahmad ; Langmuir, Peter ; Dong, Tuochuan ; Gopalakrishna, Prashanth ; Gupta, Vikas. / Long-Term survival in patients treated with ruxolitinib for myelofibrosis : COMFORT-I and-II pooled analyses. In: Journal of Hematology and Oncology. 2017 ; Vol. 10, No. 1.
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abstract = "Background: Myelofibrosis (MF) is associated with a variety of burdensome symptoms and reduced survival compared with age-/sex-matched controls. This analysis evaluated the long-Term survival benefit with ruxolitinib, a Janus kinase (JAK)1/JAK2 inhibitor, in patients with intermediate-2 (int-2) or high-risk MF. Methods: This was an exploratory analysis of 5-year data pooled from the phase 3 COMFORT-I and-II trials. In both trials, patients could cross over to ruxolitinib from the control group (COMFORT-I, placebo; COMFORT-II, best available therapy). All continuing patients in the control groups crossed over to ruxolitinib by the 3-year follow-up. Overall survival (OS; a secondary endpoint in both trials) was evaluated using pooled intent-To-Treat data from patients randomized to ruxolitinib or the control groups. OS was also evaluated in subgroups stratified by baseline anemia and transfusion status at week 24. Results: A total of 528 patients were included in this analysis; 301 were originally randomized to ruxolitinib (COMFORT-I, n = 155; COMFORT-II, n = 146) and 227 to control (n = 154 and n = 73, respectively). The risk of death was reduced by 30{\%} among patients randomized to ruxolitinib compared with patients in the control group (median OS, 5.3 vs 3.8 years, respectively; hazard ratio [HR], 0.70 [95{\%} CI, 0.54-0.91]; P = 0.0065). After correcting for crossover using a rank-preserving structural failure time (RPSFT) method, the OS advantage was more pronounced for patients who were originally randomized to ruxolitinib compared with patients who crossed over from control to ruxolitinib (median OS, 5.3 vs 2.3 years; HR [ruxolitinib vs RPSFT], 0.35 [95{\%} CI, 0.23-0.59]). An analysis of OS censoring patients at the time of crossover also demonstrated that ruxolitinib prolonged OS compared with control (median OS, 5.3 vs 2.4 years; HR [ruxolitinib vs censored at crossover], 0.53 [95{\%} CI, 0.36-0.78]; P = 0.0013). The survival benefit with ruxolitinib was observed irrespective of baseline anemia status or transfusion requirements at week 24. Conclusions: These findings support ruxolitinib treatment for patients with int-2 or high-risk MF, regardless of anemia or transfusion status. Further analyses will be important for exploring ruxolitinib earlier in the disease course to assess the effect on the natural history of MF. Trial registration: ClinicalTrials.gov identifiers, NCT00952289 and NCT00934544.",
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TY - JOUR

T1 - Long-Term survival in patients treated with ruxolitinib for myelofibrosis

T2 - COMFORT-I and-II pooled analyses

AU - Verstovsek, Srdan

AU - Gotlib, Jason

AU - Mesa, Ruben A.

AU - Vannucchi, Alessandro M.

AU - Kiladjian, Jean Jacques

AU - Cervantes, Francisco

AU - Harrison, Claire N.

AU - Paquette, Ronald

AU - Sun, William

AU - Naim, Ahmad

AU - Langmuir, Peter

AU - Dong, Tuochuan

AU - Gopalakrishna, Prashanth

AU - Gupta, Vikas

PY - 2017/9/29

Y1 - 2017/9/29

N2 - Background: Myelofibrosis (MF) is associated with a variety of burdensome symptoms and reduced survival compared with age-/sex-matched controls. This analysis evaluated the long-Term survival benefit with ruxolitinib, a Janus kinase (JAK)1/JAK2 inhibitor, in patients with intermediate-2 (int-2) or high-risk MF. Methods: This was an exploratory analysis of 5-year data pooled from the phase 3 COMFORT-I and-II trials. In both trials, patients could cross over to ruxolitinib from the control group (COMFORT-I, placebo; COMFORT-II, best available therapy). All continuing patients in the control groups crossed over to ruxolitinib by the 3-year follow-up. Overall survival (OS; a secondary endpoint in both trials) was evaluated using pooled intent-To-Treat data from patients randomized to ruxolitinib or the control groups. OS was also evaluated in subgroups stratified by baseline anemia and transfusion status at week 24. Results: A total of 528 patients were included in this analysis; 301 were originally randomized to ruxolitinib (COMFORT-I, n = 155; COMFORT-II, n = 146) and 227 to control (n = 154 and n = 73, respectively). The risk of death was reduced by 30% among patients randomized to ruxolitinib compared with patients in the control group (median OS, 5.3 vs 3.8 years, respectively; hazard ratio [HR], 0.70 [95% CI, 0.54-0.91]; P = 0.0065). After correcting for crossover using a rank-preserving structural failure time (RPSFT) method, the OS advantage was more pronounced for patients who were originally randomized to ruxolitinib compared with patients who crossed over from control to ruxolitinib (median OS, 5.3 vs 2.3 years; HR [ruxolitinib vs RPSFT], 0.35 [95% CI, 0.23-0.59]). An analysis of OS censoring patients at the time of crossover also demonstrated that ruxolitinib prolonged OS compared with control (median OS, 5.3 vs 2.4 years; HR [ruxolitinib vs censored at crossover], 0.53 [95% CI, 0.36-0.78]; P = 0.0013). The survival benefit with ruxolitinib was observed irrespective of baseline anemia status or transfusion requirements at week 24. Conclusions: These findings support ruxolitinib treatment for patients with int-2 or high-risk MF, regardless of anemia or transfusion status. Further analyses will be important for exploring ruxolitinib earlier in the disease course to assess the effect on the natural history of MF. Trial registration: ClinicalTrials.gov identifiers, NCT00952289 and NCT00934544.

AB - Background: Myelofibrosis (MF) is associated with a variety of burdensome symptoms and reduced survival compared with age-/sex-matched controls. This analysis evaluated the long-Term survival benefit with ruxolitinib, a Janus kinase (JAK)1/JAK2 inhibitor, in patients with intermediate-2 (int-2) or high-risk MF. Methods: This was an exploratory analysis of 5-year data pooled from the phase 3 COMFORT-I and-II trials. In both trials, patients could cross over to ruxolitinib from the control group (COMFORT-I, placebo; COMFORT-II, best available therapy). All continuing patients in the control groups crossed over to ruxolitinib by the 3-year follow-up. Overall survival (OS; a secondary endpoint in both trials) was evaluated using pooled intent-To-Treat data from patients randomized to ruxolitinib or the control groups. OS was also evaluated in subgroups stratified by baseline anemia and transfusion status at week 24. Results: A total of 528 patients were included in this analysis; 301 were originally randomized to ruxolitinib (COMFORT-I, n = 155; COMFORT-II, n = 146) and 227 to control (n = 154 and n = 73, respectively). The risk of death was reduced by 30% among patients randomized to ruxolitinib compared with patients in the control group (median OS, 5.3 vs 3.8 years, respectively; hazard ratio [HR], 0.70 [95% CI, 0.54-0.91]; P = 0.0065). After correcting for crossover using a rank-preserving structural failure time (RPSFT) method, the OS advantage was more pronounced for patients who were originally randomized to ruxolitinib compared with patients who crossed over from control to ruxolitinib (median OS, 5.3 vs 2.3 years; HR [ruxolitinib vs RPSFT], 0.35 [95% CI, 0.23-0.59]). An analysis of OS censoring patients at the time of crossover also demonstrated that ruxolitinib prolonged OS compared with control (median OS, 5.3 vs 2.4 years; HR [ruxolitinib vs censored at crossover], 0.53 [95% CI, 0.36-0.78]; P = 0.0013). The survival benefit with ruxolitinib was observed irrespective of baseline anemia status or transfusion requirements at week 24. Conclusions: These findings support ruxolitinib treatment for patients with int-2 or high-risk MF, regardless of anemia or transfusion status. Further analyses will be important for exploring ruxolitinib earlier in the disease course to assess the effect on the natural history of MF. Trial registration: ClinicalTrials.gov identifiers, NCT00952289 and NCT00934544.

KW - Anemia

KW - Myelofibrosis

KW - Overall survival

KW - Ruxolitinib

KW - Transfusion

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