LONG-TERM OUTCOMES OF RUXOLITINIB (RUX) THERAPY IN PATIENTS (PTS) WITH MYELOFIBROSIS (MF): 5-YEAR FINAL EFFICACY AND SAFETY ANALYSIS FROM COMFORT-I
(Abstract release date: 05/19/16)
EHA Library. Verstovsek S. 06/11/16; 135208; S452
Dr. Srdan Verstovsek
Contributions
Contributions
Abstract
Abstract: S452
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 11:30 - 11:45
Location: Hall A3
Background
The JAK1/JAK2 inhibitor RUX has demonstrated rapid and durable improvements in splenomegaly and symptoms and improved survival in the two phase 3 COMFORT studies in pts with MF.
Aims
To report final long-term efficacy and safety results after 5 years (y) of RUX treatment in COMFORT-I.
Methods
In COMFORT-I, 309 pts were randomized (1:1) to RUX or placebo (PBO). RUX starting dose was based on baseline platelet count (100–200×109/L: 15 mg BID; >200×109/L: 20 mg BID). Pts receiving PBO could crossover to RUX after the primary analysis (when all pts completed week [wk] 24 and half completed wk 36) or at any time if they had prespecified worsening of splenomegaly. The primary endpoint was the proportion of pts achieving ≥35% reduction in spleen volume (SV) at wk 24. Overall survival (OS) was estimated by Kaplan-Meier analysis according to randomized treatment (intent-to-treat analysis).
Results
Median follow-up was 268 wk at the time of this analysis. Of 155 pts randomized to RUX, 43 were still on treatment at the time of study termination. Of 154 pts randomized to PBO, 111 crossed over to RUX; median time to crossover was 41.1 wk; 28 were still on treatment at the time of study termination. At wk 24, pts originally randomized to RUX had a mean SV reduction from baseline of 31.6%; this response was durable for pts who continued on RUX with a mean SV reduction of 37.6% at wk 264. At wk 264, 18.5% of pts randomized to RUX had a ≥35% reduction from baseline in spleen volume. Median duration of spleen response (≥35% SV reduction) was 168.3 wk for RUX (range, 107.7–NE; n=92 pts). OS favored RUX (HR=0.69; 95% CI: 0.50, 0.96; P=0.025), with 69 and 82 deaths among pts originally randomized to RUX and PBO, respectively. Median OS has not been reached for pts in the RUX group. Median OS was approximately 108 wk for pts randomized to PBO censored at crossover, and approximately 200 wk for PBO pts. Mean platelet count and hemoglobin (Hgb) initially decreased through 3 mo. Mean Hgb gradually increased toward baseline. After wk 24, mean Hgb and platelet count generally remain stable through 5 y. New onset grade 3 or 4 anemia was 25.2% for the RUX arm and 26.1% for PBO crossover; grade 3 or 4 thrombocytopenia occurred in 12.3% and 13.5% of pts, respectively. Notable AEs included herpes zoster (10.3% and 13.5% of RUX and PBO crossover pts, respectively); basal cell carcinoma (7.7% and 9.0%, respectively); acute myeloid leukemia (5 pts in each arm). The rate of leukemic transformation was 0.01 per pt-year for pts randomized to RUX and 0.02 per pt-year for the PBO crossover pts.
Conclusion
After a median follow-up of 268 wk, the hazard ratio for OS favored pts randomized to RUX over those randomized to PBO, and SV reductions were sustained with long-term therapy. Collectively, these data support the durable efficacy and long-term safety of RUX in pts with MF.
Session topic: Myeloproliferative neoplasms - Clinical 2
Keyword(s): Clinical trial, Long-term follow-up, Myelofibrosis, Phase III
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 11:30 - 11:45
Location: Hall A3
Background
The JAK1/JAK2 inhibitor RUX has demonstrated rapid and durable improvements in splenomegaly and symptoms and improved survival in the two phase 3 COMFORT studies in pts with MF.
Aims
To report final long-term efficacy and safety results after 5 years (y) of RUX treatment in COMFORT-I.
Methods
In COMFORT-I, 309 pts were randomized (1:1) to RUX or placebo (PBO). RUX starting dose was based on baseline platelet count (100–200×109/L: 15 mg BID; >200×109/L: 20 mg BID). Pts receiving PBO could crossover to RUX after the primary analysis (when all pts completed week [wk] 24 and half completed wk 36) or at any time if they had prespecified worsening of splenomegaly. The primary endpoint was the proportion of pts achieving ≥35% reduction in spleen volume (SV) at wk 24. Overall survival (OS) was estimated by Kaplan-Meier analysis according to randomized treatment (intent-to-treat analysis).
Results
Median follow-up was 268 wk at the time of this analysis. Of 155 pts randomized to RUX, 43 were still on treatment at the time of study termination. Of 154 pts randomized to PBO, 111 crossed over to RUX; median time to crossover was 41.1 wk; 28 were still on treatment at the time of study termination. At wk 24, pts originally randomized to RUX had a mean SV reduction from baseline of 31.6%; this response was durable for pts who continued on RUX with a mean SV reduction of 37.6% at wk 264. At wk 264, 18.5% of pts randomized to RUX had a ≥35% reduction from baseline in spleen volume. Median duration of spleen response (≥35% SV reduction) was 168.3 wk for RUX (range, 107.7–NE; n=92 pts). OS favored RUX (HR=0.69; 95% CI: 0.50, 0.96; P=0.025), with 69 and 82 deaths among pts originally randomized to RUX and PBO, respectively. Median OS has not been reached for pts in the RUX group. Median OS was approximately 108 wk for pts randomized to PBO censored at crossover, and approximately 200 wk for PBO pts. Mean platelet count and hemoglobin (Hgb) initially decreased through 3 mo. Mean Hgb gradually increased toward baseline. After wk 24, mean Hgb and platelet count generally remain stable through 5 y. New onset grade 3 or 4 anemia was 25.2% for the RUX arm and 26.1% for PBO crossover; grade 3 or 4 thrombocytopenia occurred in 12.3% and 13.5% of pts, respectively. Notable AEs included herpes zoster (10.3% and 13.5% of RUX and PBO crossover pts, respectively); basal cell carcinoma (7.7% and 9.0%, respectively); acute myeloid leukemia (5 pts in each arm). The rate of leukemic transformation was 0.01 per pt-year for pts randomized to RUX and 0.02 per pt-year for the PBO crossover pts.
Conclusion
After a median follow-up of 268 wk, the hazard ratio for OS favored pts randomized to RUX over those randomized to PBO, and SV reductions were sustained with long-term therapy. Collectively, these data support the durable efficacy and long-term safety of RUX in pts with MF.
Session topic: Myeloproliferative neoplasms - Clinical 2
Keyword(s): Clinical trial, Long-term follow-up, Myelofibrosis, Phase III
Abstract: S452
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 11:30 - 11:45
Location: Hall A3
Background
The JAK1/JAK2 inhibitor RUX has demonstrated rapid and durable improvements in splenomegaly and symptoms and improved survival in the two phase 3 COMFORT studies in pts with MF.
Aims
To report final long-term efficacy and safety results after 5 years (y) of RUX treatment in COMFORT-I.
Methods
In COMFORT-I, 309 pts were randomized (1:1) to RUX or placebo (PBO). RUX starting dose was based on baseline platelet count (100–200×109/L: 15 mg BID; >200×109/L: 20 mg BID). Pts receiving PBO could crossover to RUX after the primary analysis (when all pts completed week [wk] 24 and half completed wk 36) or at any time if they had prespecified worsening of splenomegaly. The primary endpoint was the proportion of pts achieving ≥35% reduction in spleen volume (SV) at wk 24. Overall survival (OS) was estimated by Kaplan-Meier analysis according to randomized treatment (intent-to-treat analysis).
Results
Median follow-up was 268 wk at the time of this analysis. Of 155 pts randomized to RUX, 43 were still on treatment at the time of study termination. Of 154 pts randomized to PBO, 111 crossed over to RUX; median time to crossover was 41.1 wk; 28 were still on treatment at the time of study termination. At wk 24, pts originally randomized to RUX had a mean SV reduction from baseline of 31.6%; this response was durable for pts who continued on RUX with a mean SV reduction of 37.6% at wk 264. At wk 264, 18.5% of pts randomized to RUX had a ≥35% reduction from baseline in spleen volume. Median duration of spleen response (≥35% SV reduction) was 168.3 wk for RUX (range, 107.7–NE; n=92 pts). OS favored RUX (HR=0.69; 95% CI: 0.50, 0.96; P=0.025), with 69 and 82 deaths among pts originally randomized to RUX and PBO, respectively. Median OS has not been reached for pts in the RUX group. Median OS was approximately 108 wk for pts randomized to PBO censored at crossover, and approximately 200 wk for PBO pts. Mean platelet count and hemoglobin (Hgb) initially decreased through 3 mo. Mean Hgb gradually increased toward baseline. After wk 24, mean Hgb and platelet count generally remain stable through 5 y. New onset grade 3 or 4 anemia was 25.2% for the RUX arm and 26.1% for PBO crossover; grade 3 or 4 thrombocytopenia occurred in 12.3% and 13.5% of pts, respectively. Notable AEs included herpes zoster (10.3% and 13.5% of RUX and PBO crossover pts, respectively); basal cell carcinoma (7.7% and 9.0%, respectively); acute myeloid leukemia (5 pts in each arm). The rate of leukemic transformation was 0.01 per pt-year for pts randomized to RUX and 0.02 per pt-year for the PBO crossover pts.
Conclusion
After a median follow-up of 268 wk, the hazard ratio for OS favored pts randomized to RUX over those randomized to PBO, and SV reductions were sustained with long-term therapy. Collectively, these data support the durable efficacy and long-term safety of RUX in pts with MF.
Session topic: Myeloproliferative neoplasms - Clinical 2
Keyword(s): Clinical trial, Long-term follow-up, Myelofibrosis, Phase III
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 11:30 - 11:45
Location: Hall A3
Background
The JAK1/JAK2 inhibitor RUX has demonstrated rapid and durable improvements in splenomegaly and symptoms and improved survival in the two phase 3 COMFORT studies in pts with MF.
Aims
To report final long-term efficacy and safety results after 5 years (y) of RUX treatment in COMFORT-I.
Methods
In COMFORT-I, 309 pts were randomized (1:1) to RUX or placebo (PBO). RUX starting dose was based on baseline platelet count (100–200×109/L: 15 mg BID; >200×109/L: 20 mg BID). Pts receiving PBO could crossover to RUX after the primary analysis (when all pts completed week [wk] 24 and half completed wk 36) or at any time if they had prespecified worsening of splenomegaly. The primary endpoint was the proportion of pts achieving ≥35% reduction in spleen volume (SV) at wk 24. Overall survival (OS) was estimated by Kaplan-Meier analysis according to randomized treatment (intent-to-treat analysis).
Results
Median follow-up was 268 wk at the time of this analysis. Of 155 pts randomized to RUX, 43 were still on treatment at the time of study termination. Of 154 pts randomized to PBO, 111 crossed over to RUX; median time to crossover was 41.1 wk; 28 were still on treatment at the time of study termination. At wk 24, pts originally randomized to RUX had a mean SV reduction from baseline of 31.6%; this response was durable for pts who continued on RUX with a mean SV reduction of 37.6% at wk 264. At wk 264, 18.5% of pts randomized to RUX had a ≥35% reduction from baseline in spleen volume. Median duration of spleen response (≥35% SV reduction) was 168.3 wk for RUX (range, 107.7–NE; n=92 pts). OS favored RUX (HR=0.69; 95% CI: 0.50, 0.96; P=0.025), with 69 and 82 deaths among pts originally randomized to RUX and PBO, respectively. Median OS has not been reached for pts in the RUX group. Median OS was approximately 108 wk for pts randomized to PBO censored at crossover, and approximately 200 wk for PBO pts. Mean platelet count and hemoglobin (Hgb) initially decreased through 3 mo. Mean Hgb gradually increased toward baseline. After wk 24, mean Hgb and platelet count generally remain stable through 5 y. New onset grade 3 or 4 anemia was 25.2% for the RUX arm and 26.1% for PBO crossover; grade 3 or 4 thrombocytopenia occurred in 12.3% and 13.5% of pts, respectively. Notable AEs included herpes zoster (10.3% and 13.5% of RUX and PBO crossover pts, respectively); basal cell carcinoma (7.7% and 9.0%, respectively); acute myeloid leukemia (5 pts in each arm). The rate of leukemic transformation was 0.01 per pt-year for pts randomized to RUX and 0.02 per pt-year for the PBO crossover pts.
Conclusion
After a median follow-up of 268 wk, the hazard ratio for OS favored pts randomized to RUX over those randomized to PBO, and SV reductions were sustained with long-term therapy. Collectively, these data support the durable efficacy and long-term safety of RUX in pts with MF.
Session topic: Myeloproliferative neoplasms - Clinical 2
Keyword(s): Clinical trial, Long-term follow-up, Myelofibrosis, Phase III
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