Controlled Myelofibrosis Study With Oral Janus-associated Kinase (JAK) Inhibitor Treatment-II: The COMFORT-II Trial

The change in spleen volume from baseline to week 48 was measured by magnetic resonance imaging (MRI) (or by computer tomography (CT) for participants unable to undergo MRI) and was calculated only for participants who had an evaluable spleen volume at baseline. The percentage of participants achieving a greater than or equal to 35% reduction in spleen volume from baseline to week 48 was then calculated by treatment group.

Time frame: Baseline, Week 48

Population: Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria. The table included participants with non-missing baseline MRI measurement of spleen volume only.

Shift table from baseline to last available postbaseline fibrosis grade by treatment The grade gives an indication of the activity or amount of inflammation and the stage represents the amount of fibrosis or scarring. The grade is assigned a number based on the degree of inflammation, which is usually scored from 0-4 with 0 being no activity and 3 or 4 considered severe activity

Time frame: Baseline, once a year

Population: Full Analysis Set (FAS)~Numbers of Participants Analyzed reflect only those participants who were randomized to either Ruxolitinib or Best Available Therapy and do not count those participants who could have crossed over to Ruxolitinib

Number of Participants with duration of Follow up

Time frame: baseline, 260 weeks (end of study)

Population: Safety Set~Numbers of Participants Analyzed reflect only those participants who were randomized to either Ruxolitinib or Best Available Therapy and do not count those participants who could have crossed over to Ruxolitinib

This is defined as the interval between randomization and date of the first MRI showing a 35% reduction from baseline in spleen volume. The analysis was performed for participants who achieved a 35% reduction in spleen volume.

Time frame: Baseline, up to Year 5

Population: Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria. Treatment groups were defined according to the treatment assignment at the time of randomization.

DoMSR is defined as the interval between the first spleen volume measurement that is \>=35% reduction from baseline and the first scan that is no longer = 35% reduction AND that is a \>25% increase over nadir. It was evaluated using the Kaplan-Meier estimate for each treatment arm. The analysis was performed only for subjects who achieved greater than 35% reduction in spleen volume.

Time frame: Baseline, up to Year 5

Population: Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria. Treatment groups were defined according to the treatment assignment at the time of randomization.

Time from randomization and earliest of either (1) date of bone marrow blast count of 20% or greater; (2) date of first peripheral blast count of 20% or greater that was subsequently confirmed to sustain for at least 8 weeks; (3) date of death from any cause

Time frame: Time from randomization and earliest of either leukemia or death

Population: Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria. Treatment groups were defined according to the treatment assignment at the time of randomization.

Defined as the interval between randomization and the date of the bone marrow blast count of 20% or greater OR the date of the first peripheral blast count of 20% or greater that was subsequently confirmed to have been sustained for at least 8 weeks OR the date of death from any cause, whichever occurs first. OS was summarized using Kaplan-Meier estimates for each treatment arm. The estimates were supplemented by tables of number of events and probability estimates at several timepoints

Time frame: From randomization until death from any cause

Population: Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria. Treatment groups were defined according to the treatment assignment at the time of randomization.

The change in spleen volume from baseline to week 24 was measured by magnetic resonance imaging (MRI) (or by computer tomography (CT) for participants unable to undergo MRI) and was calculated only for participants who had an evaluable spleen volume at baseline. The percentage of participants achieving a greater than or equal to 35% reduction in spleen volume from baseline to week 24 was then calculated by treatment group.

Time frame: Baseline, Week 24

Population: Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria. The table included participants with non-missing baseline MRI measurement of spleen volume only.

This was noted as fibrosis density and was tabulated by fibrosis grade at baseline and at week 48 (post-baseline). Descriptive statistics (participant percentages) were used. Fibrosis grades: 0 Scattered linear reticulin with no intersections corresponding to normal bone marrow ; 1 Loose network of reticulin with many intersections, especially in perivascular areas; 2 Diffuse and dense increase in reticulin with extensive intersections, occasionally with only focal bundles of collagen and/or focal osteosclerosis; 3 Diffuse and dense increase in reticulin with extensive intersections with coarse bundles of collagen, often associated with significant osteosclerosis

Time frame: 48 weeks

Population: Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria.

Median of time progression free survival (95% CI), years

Time frame: Time from randomization and the earliest of either increase in spleen volume >=25% from on-study nadir, splenic irradiation, splenectomy, leukemic transformation or death

Population: Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria. Treatment groups were defined according to the treatment assignment at the time of randomization.

This is defined as the interval between randomization and date of the first MRI showing at least 35% reduction from baseline in spleen volume. The analysis was performed for participants who achieved a 35% reduction in spleen volume

Time frame: Time from randomization and date of the first MRI showing at least 35% reduction from baseline in spleen volume

Population: Full analysis set (FAS)