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Table 1 Randomised control trials of ruxolitinib in MPN

From: The ruxolitinib effect: understanding how molecular pathogenesis and epigenetic dysregulation impact therapeutic efficacy in myeloproliferative neoplasms

TRIAL MPN Trial Endpoints Long term outcomes Significant toxicities Genomic effects 1—driver mutations Genomic effects 2—additional mutations References
COMFORT 1 PMF
Post ET-MF
Post PV-MF
Intermediate 2 or High Risk
Ruxolitinib (n = 155) v Placebo (n = 154) SVR ≥ 35% 24 weeks
 RUX = 41.9%
Placebo = 0.7%
TSS reduction ≥ 50% at 24 weeks
RUX = 45.9%
Placebo = 5.3%
Median OS
 RUX = NR
Placebo = 200 weeks
Spleen response duration
 RUX = 168.3 weeks
Grade ¾
Anaemia
 RUX = 45.2%
Placebo = 19.2%
Thrombocytopenia
 RUX = 12.9%
 Placebo = 1.3%
Neutropenia
 RUX = 7.1%
 Placebo = 2.0%
JAK2 V617F positive
 RUX = 73%
 Placebo = 80%
No difference between JAK2 V617F mutation positive or negative patients
Not available [9,10,11]
COMFORT 2 PMF
Post ET-MF
Post PV-MF
Intermediate 2 or High Risk
Ruxolitinib (n = 146) v BAT (n = 73) SVR ≥ 35% 48 weeks
 RUX = 28%
 BAT = 0%
Median OS
 RUX = NR
 BAT = 4.1 years
Spleen response duration
 RUX = 3.2 years
Grade ¾
Anaemia
 RUX = 46.1%
Thrombocytopenia
 RUX = 18.8%
Neutropenia
 RUX = 8.9%
Lymphopenia
 RUX = 31.4%
110/146 RUX. pts JAK2 V617F positive
Median allele burden = 84%
Allelle burden reduction ≥ 20% = 38.3% weeks 168
High molecular risk v low molecular risk (defined previously in [25])
SVR ≥ 35% 48 weeks
 HMR = 26.1%
 LMR = 35.0%
Mean SVR 48 weeks
 HMR = − 23.5%
 LMR = − 30.6%
 No mutation individually correlated
KM estimate Survival 144 weeks
 HMR RUX = 0.79
 HMR BAT = 0.58
 LMR RUX = 0.85
 LMR BAT = 0.71
 HMR pts have HR 0.57 (CI 0.30–1.08) of death
 No data on CALR
[13, 14]
JUMP PMF
Post ET-MF
Post PV-MF
Intermediate 1, intermediate 2 or high risk
Single arm Ruxolitinib study
(n = 1144)
SLR ≥ 50% 48 weeks
 RUX = 62.3%
Spleen response duration
 RUX = NR
OS probability at 48 weeks
 RUX = 94%
PFS probability at 48 weeks
 RUX = 91%
Grade ¾
Anameia = 33%
 Thrombocytopenia = 12.5%
 Neutropenia = 3.9%
Not available Not available [12]
RESPONSE 1 PV
HU intolerant/resistant with splenomegaly
Ruxolitinib (n = 110) v BAT (n = 112) Haematocrit control and SVR ≥ 35% 32 weeks
 RUX = 20.9%
 BAT = 0.9%
Haematocrit Control 32 weeks
 RUX = 60.0%
 BAT = 19.6%
SVR ≥ 35% 32 weeks
 RUX = 38.2%
 BAT = 0.9%
Thromboembolic rate
 RUX = 1.8/100pt years
 BAT = 8.2/100pt years
CHR at 32 weeks
 RUX = 23.6%
 BAT = 8.9%
Maintained CHR at 80 weeks
RUX = 69%
Grade 3/4 80 weeks
Anaemia
 RUX = 0.9%
Thrombocytopenia
 RUX = 2.6%
Neutropenia
 RUX = 0.4%
Lymphopenia
 RUX = 9.7%
JAK2 V617F allele burden 32 weeks
 RUX = − 12.2%
 BAT = + 1.2%
JAK2 V617F allele burden 80 weeks
 RUX = − 22.0%
JAK2 V617F allele burden 208 weeks max reduction
 RUX = − 35.9%
 Crossover = − 21.2%
CMR/PMR possible in patients with ASXL1, TET2, JAK3, SOCS1 mutations [20, 21, 26]
RESPONSE 2 PV
HU intolerant/resistant without splenomegaly
Ruxolitinib (n = 74) v BAT (n = 75) Haematocrit control 28 weeks
 RUX = 62%
 BAT = 19%
Maintenance haematocrit response
 RUX = 78%
CHR Maintained at 80 weeks
 RUX = 24.3%
 BAT = 2.7%
TSS reduction ≥ 50% 80 weeks
 RUX = 45%
Grade 3/4 80 weeks
Anaemia
 RUX = 0%
Thrombocytopenia
 RUX = 0%
Hypertension
 RUX = 6.8%
 BAT = 5.7%
JAK2 V617F Burden 28 weeks
 RUX = − 4.7%
 BAT = − 2.0%
JAK2 V617F Burden 80 weeks
 RUX = − 9.7%
Not available [18, 19]
MAJIC ET ET
HU intolerant/resistant
Ruxolitinib (n = 58) v BAT (n = 52) Complete response within 1 year
 RUX = 46.6%
 BAT = 44.2%
Thromboembolic events in 2 years
 RUX = 17.2%
 BAT = 5.8%
  JAK2 V617F Burden
 No change in mean allele burden in either treatment arm
Not available [22]
  1. CHR complete haematological remission, CMR complete molecular response, HMR high molecular risk, KM Kaplan Meier, NR not reached, LMR low molecular risk, OS overall survival, PFS progression free survival, PMR partial molecular response, SLR spleen length response,SVR spleen volume response, TSS total symptom score