Patients with primary or secondary myelofibrosis who developed new or worsening anemia after frontline Jakafi (ruxolitinib) treatment did not experience poorer outcomes because of the anemia, according to findings of the phase 3b JUMP trial.
Myelofibrosis is a type of cancer that causes bone marrow scarring, which can prevent adequate production of healthy red blood cells (hemoglobin). This condition is called anemia and can sometimes lead to patients relying on blood transfusions to maintain healthy hemoglobin levels.
MORE: Management of Anemia in Patients With Myelofibrosis
The median overall survival (OS; time from treatment until death of any cause) among patients who had worsening anemia (361 patients) was 58.3 months compared with not evaluable in those with baseline (start of the study) anemia that didn’t worsen (486 patients). The median OS for patients with anemia that did not worsen was not evaluable because not enough patients had died for the researchers to calculate an average time until death.
Similarly, patients who did not have anemia at baseline who developed anemia (756 patients) and those who did not develop anemia (630 patients) both had OS medians that were not evaluable.
In a poster presentation of the data at the European Hematology Association Annual Congress, study authors noted that these findings were consistent with the results of a recent pooled data analysis of the phase 3 COMFORT-I and COMFORT-II studies, which both examined Jakafi for patients with myelofibrosis.
“Dose-dependent anemia is one of the [side effects] of [Jakafi] therapy,” Dr. Haifa Kathrin Al-Ali, lead study author, professor of hematology, and head of the Krukenberg Cancer Center, at the University Hospital Halle (Saale) in Germany, explained during the presentation. “A previous analysis of two phase 3 trials [showed that] new or worsening anemia did not diminish the clinical benefit of [Jakafi] therapy.”
“The objective of this current analysis was to validate these findings using data from JUMP, which is the largest trial [of Jakafi] in patients with myelofibrosis to date,” he explained.
Comparing Spleen Reduction and Quality of Life
The percentage of evaluable patients who, at week 24, experienced a spleen size reduction of 50% or more were:
- 31.5% in patients without anemia baseline who developed anemia,
- 31.2% in patients without anemia at baseline who did not develop anemia,
- 24.4% in patients with anemia at baseline whose anemia worsened and did not require blood transfusions,
- 27.9% in patients with anemia at baseline whose anemia did not worsen and did not require blood transfusions,
- 25% in patients with anemia at baseline that worsened and required blood transfusions and
- 29.8% in patients with baseline anemia that did not worsen and required blood transfusions.
At week 48, evaluable patients without anemia at baseline in the new or worsening anemia group (289 patients) and the no new or worsening anemia group (257 patients) experienced a spleen length reduction of at least 50% at respective rates of 35.6% versus 26.1%. These respective spleen reduction rates were 29.6% versus 27.2% in not worsening and worsening anemia groups, respectively who all had anemia at baseline and did not require blood transfusions. Nineteen percent and 33.3% of patients who had anemia at baseline and had worsening and non-worsening anemia, respectively, experienced a spleen reduction of at least 50%. The difference was not statistically significant.
In the non-transfusion requiring anemia subgroup 81 patients experienced new or worsening anemia and 103 did not; these figures were 58 patients and 45 patients, respectively in the transfusion-requiring anemia subgroup.
Researchers compared symptom responses at 24 weeks among patients with and without anemia at baseline and who went on to develop (or not develop) anemia during treatment.
In terms of symptom response, at week 24, patients who were not anemic at baseline in the new or worsening anemia group (618 patients) and the no new or worsening anemia group (530 patients) achieved a minimum 6.5-point increase in FACT-Lym total score at respective rates of 34.5% versus 34%; these respective rates were 32.7% versus 29.6% and 41.7% versus 32.1% among patients with non-transfusion requiring anemia and transfusion-requiring anemia. There was no statistically significant difference between any of these findings.
In the non-transfusion requiring anemia subgroup, 153 patients experienced new or worsening anemia and 243 did not; these figures were 120 and 109 patients, respectively in the transfusion-requiring anemia subgroup.
Health-related quality of life was measured with the FACT-Lym, a 42-item survey that measures aspects of physical, social, emotional and functional well-being.
At week 48, patients without anemia at baseline in the new or worsening anemia group (120 patients) and the no new or worsening anemia group (109 patients) experienced a minimum 6.5-point increase in FACT-Lym total score (which indicates worsening in quality of life) at respective rates of 30.4% versus 23.3%. These respective rates were 26.4% versus 27.6% and 34.2% versus 33.3% among patients with non-transfusion requiring anemia and transfusion-requiring anemia.
In those with non-transfusion requiring anemia subgroup, 106 patients experienced new or worsening anemia and 156 did not; these figures were 79 and 66 patients, respectively in the transfusion-requiring anemia subgroup.
Among evaluable patients in the new or worsening anemia (1,033 patients) and no new or worsening anemia group (1,000 patients) received a median dose exposure of 12.2 months and 12.5 months with Jakafi, respectively.
“These results are consistent with those obtained from a previous pooled analysis from the 2 phase 3 COMFORT trials,” Al-Ali concluded. “These results from JUMP … support the use of [Jakafi] in patients with myelofibrosis regardless of baseline anemia or the development of treatment-related anemia.”
About the JUMP Trial
JUMP is a global study that evaluated Jakafi treatment in patients with myelofibrosis. In order to be eligible, patients needed to be at least 18 years old and have a diagnosis of primary or secondary myelofibrosis that is high-, intermediate-2 or intermediate-1 risk according to International Prognostic Scoring System (IPSS) criteria. The IPSS criteria is a list of prognostic factors, such as age, hemoglobin levels and symptoms, that helps clinicians determine risk categories for patients with the disease. Patients with intermediate-1 risk disease must have palpable splenomegaly (inflammation of the spleen) of at least 5 centimeters from the costal margin.
The main goal of JUMP was evaluating safety. Secondary end points (results measured at the end of a study) included the percentage of participants with at least 50% reduction in spleen length, five-year best overall response according to spleen length, and change in ECOG performance status (which rates patients based on how independent they are in performing their daily tasks) from baseline to worst post-baseline up to five years.
The baseline characteristics of the new or worsening anemia (1,117 patients) and no new or worsening anemia (1,116 patients) groups were generally well balanced, according to the researchers.
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