RUXOLITINIB (RUX) REDUCES JAK2V617F ALLELE BURDEN (AB) IN PATIENTS (PTS) WITH POLYCYTHEMIA VERA (PV) ENROLLED IN THE RESPONSE STUDY
(Abstract release date: 05/19/16)
EHA Library. Vannucchi A. 06/11/16; 135210; S454
Prof. Alessandro M. Vannucchi
Contributions
Contributions
Abstract
Abstract: S454
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 12:00 - 12:15
Location: Hall A3
Background
The JAK2V617F mutation leads to constitutive activation of downstream JAK/STAT signaling in pts with PV. In the phase 3 RESPONSE study evaluating Rux (an oral JAK1/JAK2 inhibitor) vs best available therapy (BAT) in pts with PV who had an inadequate response to or unacceptable side effects from hydroxyurea, Rux was superior to BAT in controlling hematocrit, reducing spleen volume, and improving symptoms. Rux also decreased JAK2V617F AB steadily over time up to Week 112.
Aims
This follow-up exploratory analysis of the RESPONSE study evaluated the effect of long-term Rux treatment on JAK2V617F AB in pts with PV.
Methods
211 pts with the JAK2V617F mutation at Baseline were evaluable for this analysis. AB was defined as the percent of mutant allele relative to total (wild-type and mutant). Changes from Baseline in JAK2V617F AB among Rux-randomized pts and those who crossed over from BAT to Rux were reported up to Week 208. Baseline AB for the crossover cohort was defined as last observation before receiving Rux. Complete and partial molecular remission (CMR, PMR) were defined using the IWG-MRT/ELN consensus criteria. An exploratory analysis was performed to identify any potential relationship between reductions in AB and spleen volume.
Results
Pts randomized to Rux (n=104) experienced consistent AB reduction (mean percent change from Baseline, –12.2%, –18.3%, –22.0%, –30.0%, –38.1%, –34.9%, and –40.0% at Weeks 32, 56, 80, 112, 144, 176, and 208, respectively). On average, BAT-randomized pts did not experience AB improvements at Week 32 (mean percent change from Baseline, 1.2%); those who crossed over to Rux (n=80) had markedly reduced AB over time (–6.3%, –6.7%, –10.4%, –15.7%, –17.8%, and –13.0% at 32, 56, 80, 112, 144, and 176 weeks after crossover, respectively). Mean baseline AB for pts who did and did not have prior interferon (IFN) therapy was as follows: Rux: IFN=72.1%, no IFN=74.5%; BAT: IFN=88.2%, no IFN=72.0%. All BAT pts who received IFN (n=13) at randomization crossed over to Rux; mean maximal AB reduction in evaluable BAT pts receiving IFN was –6.6% before crossover and –25.6% after crossover. The average maximal percent reductions in AB (median time to maximal reduction) in Rux-randomized and Rux crossover arms were –35.9% (25.9 mo) and –21.2% (18.2 mo), respectively (Figure). Among evaluable pts, 2/102 (2.0%) Rux-randomized pts achieved CMR at Weeks 143 and 144 vs 1/94 (1.1%) Rux crossover pts at Week 123. Pts who achieved PMR included 33/101 (32.7%) evaluable Rux-randomized pts and 20/92 (21.7%) evaluable Rux crossover pts, after median times of 112 and 92 weeks, respectively. Seven pts had ≥90% AB reduction from Baseline (Rux-randomized, n=6; Rux crossover, n=1). Based on tertiles of maximal AB reduction for the Rux-randomized arm, there was no relationship between mean maximal change in AB (tertile 1, –72.2%; tertile 2, –29.1%; tertile 3, –5.7%) and mean PV duration (mo) from diagnosis (tertile 1, 81.6; tertile 2, 126.2; tertile 3, 105.2). No linear relationship was observed at last visit between percent change in AB from Baseline and corresponding clinical outcomes in terms of spleen volume reduction.
Conclusion
Rux treatment (randomized and post-crossover) reduced JAK2V617F AB in RESPONSE study pts after up to 4 years of treatment. Some pts may experience molecular responses with Rux treatment regardless of initiation timing during the disease course or previous IFN treatment. No clear relationship between AB reduction and spleen volume reduction was observed.
Session topic: Myeloproliferative neoplasms - Clinical 2
Keyword(s): Molecular response, Myeloproliferative disorder, Polycythemia vera
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 12:00 - 12:15
Location: Hall A3
Background
The JAK2V617F mutation leads to constitutive activation of downstream JAK/STAT signaling in pts with PV. In the phase 3 RESPONSE study evaluating Rux (an oral JAK1/JAK2 inhibitor) vs best available therapy (BAT) in pts with PV who had an inadequate response to or unacceptable side effects from hydroxyurea, Rux was superior to BAT in controlling hematocrit, reducing spleen volume, and improving symptoms. Rux also decreased JAK2V617F AB steadily over time up to Week 112.
Aims
This follow-up exploratory analysis of the RESPONSE study evaluated the effect of long-term Rux treatment on JAK2V617F AB in pts with PV.
Methods
211 pts with the JAK2V617F mutation at Baseline were evaluable for this analysis. AB was defined as the percent of mutant allele relative to total (wild-type and mutant). Changes from Baseline in JAK2V617F AB among Rux-randomized pts and those who crossed over from BAT to Rux were reported up to Week 208. Baseline AB for the crossover cohort was defined as last observation before receiving Rux. Complete and partial molecular remission (CMR, PMR) were defined using the IWG-MRT/ELN consensus criteria. An exploratory analysis was performed to identify any potential relationship between reductions in AB and spleen volume.
Results
Pts randomized to Rux (n=104) experienced consistent AB reduction (mean percent change from Baseline, –12.2%, –18.3%, –22.0%, –30.0%, –38.1%, –34.9%, and –40.0% at Weeks 32, 56, 80, 112, 144, 176, and 208, respectively). On average, BAT-randomized pts did not experience AB improvements at Week 32 (mean percent change from Baseline, 1.2%); those who crossed over to Rux (n=80) had markedly reduced AB over time (–6.3%, –6.7%, –10.4%, –15.7%, –17.8%, and –13.0% at 32, 56, 80, 112, 144, and 176 weeks after crossover, respectively). Mean baseline AB for pts who did and did not have prior interferon (IFN) therapy was as follows: Rux: IFN=72.1%, no IFN=74.5%; BAT: IFN=88.2%, no IFN=72.0%. All BAT pts who received IFN (n=13) at randomization crossed over to Rux; mean maximal AB reduction in evaluable BAT pts receiving IFN was –6.6% before crossover and –25.6% after crossover. The average maximal percent reductions in AB (median time to maximal reduction) in Rux-randomized and Rux crossover arms were –35.9% (25.9 mo) and –21.2% (18.2 mo), respectively (Figure). Among evaluable pts, 2/102 (2.0%) Rux-randomized pts achieved CMR at Weeks 143 and 144 vs 1/94 (1.1%) Rux crossover pts at Week 123. Pts who achieved PMR included 33/101 (32.7%) evaluable Rux-randomized pts and 20/92 (21.7%) evaluable Rux crossover pts, after median times of 112 and 92 weeks, respectively. Seven pts had ≥90% AB reduction from Baseline (Rux-randomized, n=6; Rux crossover, n=1). Based on tertiles of maximal AB reduction for the Rux-randomized arm, there was no relationship between mean maximal change in AB (tertile 1, –72.2%; tertile 2, –29.1%; tertile 3, –5.7%) and mean PV duration (mo) from diagnosis (tertile 1, 81.6; tertile 2, 126.2; tertile 3, 105.2). No linear relationship was observed at last visit between percent change in AB from Baseline and corresponding clinical outcomes in terms of spleen volume reduction.
Conclusion
Rux treatment (randomized and post-crossover) reduced JAK2V617F AB in RESPONSE study pts after up to 4 years of treatment. Some pts may experience molecular responses with Rux treatment regardless of initiation timing during the disease course or previous IFN treatment. No clear relationship between AB reduction and spleen volume reduction was observed.
Session topic: Myeloproliferative neoplasms - Clinical 2
Keyword(s): Molecular response, Myeloproliferative disorder, Polycythemia vera
Abstract: S454
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 12:00 - 12:15
Location: Hall A3
Background
The JAK2V617F mutation leads to constitutive activation of downstream JAK/STAT signaling in pts with PV. In the phase 3 RESPONSE study evaluating Rux (an oral JAK1/JAK2 inhibitor) vs best available therapy (BAT) in pts with PV who had an inadequate response to or unacceptable side effects from hydroxyurea, Rux was superior to BAT in controlling hematocrit, reducing spleen volume, and improving symptoms. Rux also decreased JAK2V617F AB steadily over time up to Week 112.
Aims
This follow-up exploratory analysis of the RESPONSE study evaluated the effect of long-term Rux treatment on JAK2V617F AB in pts with PV.
Methods
211 pts with the JAK2V617F mutation at Baseline were evaluable for this analysis. AB was defined as the percent of mutant allele relative to total (wild-type and mutant). Changes from Baseline in JAK2V617F AB among Rux-randomized pts and those who crossed over from BAT to Rux were reported up to Week 208. Baseline AB for the crossover cohort was defined as last observation before receiving Rux. Complete and partial molecular remission (CMR, PMR) were defined using the IWG-MRT/ELN consensus criteria. An exploratory analysis was performed to identify any potential relationship between reductions in AB and spleen volume.
Results
Pts randomized to Rux (n=104) experienced consistent AB reduction (mean percent change from Baseline, –12.2%, –18.3%, –22.0%, –30.0%, –38.1%, –34.9%, and –40.0% at Weeks 32, 56, 80, 112, 144, 176, and 208, respectively). On average, BAT-randomized pts did not experience AB improvements at Week 32 (mean percent change from Baseline, 1.2%); those who crossed over to Rux (n=80) had markedly reduced AB over time (–6.3%, –6.7%, –10.4%, –15.7%, –17.8%, and –13.0% at 32, 56, 80, 112, 144, and 176 weeks after crossover, respectively). Mean baseline AB for pts who did and did not have prior interferon (IFN) therapy was as follows: Rux: IFN=72.1%, no IFN=74.5%; BAT: IFN=88.2%, no IFN=72.0%. All BAT pts who received IFN (n=13) at randomization crossed over to Rux; mean maximal AB reduction in evaluable BAT pts receiving IFN was –6.6% before crossover and –25.6% after crossover. The average maximal percent reductions in AB (median time to maximal reduction) in Rux-randomized and Rux crossover arms were –35.9% (25.9 mo) and –21.2% (18.2 mo), respectively (Figure). Among evaluable pts, 2/102 (2.0%) Rux-randomized pts achieved CMR at Weeks 143 and 144 vs 1/94 (1.1%) Rux crossover pts at Week 123. Pts who achieved PMR included 33/101 (32.7%) evaluable Rux-randomized pts and 20/92 (21.7%) evaluable Rux crossover pts, after median times of 112 and 92 weeks, respectively. Seven pts had ≥90% AB reduction from Baseline (Rux-randomized, n=6; Rux crossover, n=1). Based on tertiles of maximal AB reduction for the Rux-randomized arm, there was no relationship between mean maximal change in AB (tertile 1, –72.2%; tertile 2, –29.1%; tertile 3, –5.7%) and mean PV duration (mo) from diagnosis (tertile 1, 81.6; tertile 2, 126.2; tertile 3, 105.2). No linear relationship was observed at last visit between percent change in AB from Baseline and corresponding clinical outcomes in terms of spleen volume reduction.
Conclusion
Rux treatment (randomized and post-crossover) reduced JAK2V617F AB in RESPONSE study pts after up to 4 years of treatment. Some pts may experience molecular responses with Rux treatment regardless of initiation timing during the disease course or previous IFN treatment. No clear relationship between AB reduction and spleen volume reduction was observed.
Session topic: Myeloproliferative neoplasms - Clinical 2
Keyword(s): Molecular response, Myeloproliferative disorder, Polycythemia vera
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 12:00 - 12:15
Location: Hall A3
Background
The JAK2V617F mutation leads to constitutive activation of downstream JAK/STAT signaling in pts with PV. In the phase 3 RESPONSE study evaluating Rux (an oral JAK1/JAK2 inhibitor) vs best available therapy (BAT) in pts with PV who had an inadequate response to or unacceptable side effects from hydroxyurea, Rux was superior to BAT in controlling hematocrit, reducing spleen volume, and improving symptoms. Rux also decreased JAK2V617F AB steadily over time up to Week 112.
Aims
This follow-up exploratory analysis of the RESPONSE study evaluated the effect of long-term Rux treatment on JAK2V617F AB in pts with PV.
Methods
211 pts with the JAK2V617F mutation at Baseline were evaluable for this analysis. AB was defined as the percent of mutant allele relative to total (wild-type and mutant). Changes from Baseline in JAK2V617F AB among Rux-randomized pts and those who crossed over from BAT to Rux were reported up to Week 208. Baseline AB for the crossover cohort was defined as last observation before receiving Rux. Complete and partial molecular remission (CMR, PMR) were defined using the IWG-MRT/ELN consensus criteria. An exploratory analysis was performed to identify any potential relationship between reductions in AB and spleen volume.
Results
Pts randomized to Rux (n=104) experienced consistent AB reduction (mean percent change from Baseline, –12.2%, –18.3%, –22.0%, –30.0%, –38.1%, –34.9%, and –40.0% at Weeks 32, 56, 80, 112, 144, 176, and 208, respectively). On average, BAT-randomized pts did not experience AB improvements at Week 32 (mean percent change from Baseline, 1.2%); those who crossed over to Rux (n=80) had markedly reduced AB over time (–6.3%, –6.7%, –10.4%, –15.7%, –17.8%, and –13.0% at 32, 56, 80, 112, 144, and 176 weeks after crossover, respectively). Mean baseline AB for pts who did and did not have prior interferon (IFN) therapy was as follows: Rux: IFN=72.1%, no IFN=74.5%; BAT: IFN=88.2%, no IFN=72.0%. All BAT pts who received IFN (n=13) at randomization crossed over to Rux; mean maximal AB reduction in evaluable BAT pts receiving IFN was –6.6% before crossover and –25.6% after crossover. The average maximal percent reductions in AB (median time to maximal reduction) in Rux-randomized and Rux crossover arms were –35.9% (25.9 mo) and –21.2% (18.2 mo), respectively (Figure). Among evaluable pts, 2/102 (2.0%) Rux-randomized pts achieved CMR at Weeks 143 and 144 vs 1/94 (1.1%) Rux crossover pts at Week 123. Pts who achieved PMR included 33/101 (32.7%) evaluable Rux-randomized pts and 20/92 (21.7%) evaluable Rux crossover pts, after median times of 112 and 92 weeks, respectively. Seven pts had ≥90% AB reduction from Baseline (Rux-randomized, n=6; Rux crossover, n=1). Based on tertiles of maximal AB reduction for the Rux-randomized arm, there was no relationship between mean maximal change in AB (tertile 1, –72.2%; tertile 2, –29.1%; tertile 3, –5.7%) and mean PV duration (mo) from diagnosis (tertile 1, 81.6; tertile 2, 126.2; tertile 3, 105.2). No linear relationship was observed at last visit between percent change in AB from Baseline and corresponding clinical outcomes in terms of spleen volume reduction.
Conclusion
Rux treatment (randomized and post-crossover) reduced JAK2V617F AB in RESPONSE study pts after up to 4 years of treatment. Some pts may experience molecular responses with Rux treatment regardless of initiation timing during the disease course or previous IFN treatment. No clear relationship between AB reduction and spleen volume reduction was observed.
Session topic: Myeloproliferative neoplasms - Clinical 2
Keyword(s): Molecular response, Myeloproliferative disorder, Polycythemia vera
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