Table 1 Randomised control trials of ruxolitinib in MPN
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 | |
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 | |
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 | |
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 | |
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] |