Meds for anemia let myelofibrosis patients stay on cancer drug, per trial
Add-on treatment allows Jakavi use at full-strength, without losing its benefits
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Giving myelofibrosis trial participants medications for anemia allowed them to continue taking the approved cancer therapy Jakavi, sold in the U.S. as Jakafi, at full strength. (Image from iStock)
Adding medications to combat anemia to treatment with the approved myelofibrosis drug Jakavi (ruxolitinib), sold as Jakafi in the U.S., allowed patients with low red blood cell levels taking part in a late-stage clinical trial to remain on full-strength cancer treatment without losing the therapy’s key benefits.
That’s according to a new analysis, conducted after the trial’s completion, that showed that the use of meds for anemia — a condition marked by low levels of oxygen-carrying red blood cells or the iron-rich protein hemoglobin — helped maintain the full benefits of Jakavi treatment. While Jakavai effectively reduces spleen size and disease symptoms in people with this rare blood cancer, the medication itself can cause or worsen anemia among patients.
These new findings come from a post hoc analysis — one conducted after a study has concluded — of a Phase 3b trial dubbed JUMP (NCT01493414), which altogether enrolled more than 2,000 people diagnosed with intermediate- or high-risk myelofibrosis. About 40% of the participants had pronounced anemia at the study’s start. This analysis covered 101 individuals with myelofibrosis and anemia given anemia meds within the first three months, and also included more than 1,000 participants with that complication who did not receive any additional treatment.
According to the researchers, the results suggest “that patients treated with [Jakavi] and anemia-[targeted] care … [show] symptom response rates … comparable to the overall JUMP population.” The team noted that the majority of the trial’s participants did not have pronounced anemia.
The study, “Outcomes of patients with myelofibrosis treated with ruxolitinib and anemia-supporting medications,” was published in the journal Hematology.
In myelofibrosis, a type of chronic blood cancer, abnormal blood cells are produced in the bone marrow, the spongy center of certain bones. This results in the accumulation of scar tissue, interferes with the production of healthy blood cells, and leads to symptoms that typically include an enlarged spleen, fatigue, and weight loss.
Anemia, which can be life-threatening in severe cases, affects about one-third of people with myelofibrosis at diagnosis and usually worsens as the disease progresses. Use of Jakavi, approved more than a decade ago as a treatment for myelofibrosis, also can cause or worsen anemia.
Analysis looked at data from over 1,300 trial participants
Among individuals with cancer and anemia, medications known as erythropoiesis-stimulating agents (ESAs) — synthetic versions of erythropoietin, a natural hormone that stimulates red blood cell production — and danazol, a synthetic version of androgen (a testosterone derivative), may help manage anemia alongside disease-directed treatment.
In this analysis, the researchers reviewed data from the JUMP trial to evaluate the addition of anemia-targeted medications to Jakavi in patients with both conditions.
The trial involved 2,233 adults with myelofibrosis, slightly more men than women, with a median age of 67. Among the participants, 69% overall had anemia, defined as hemoglobin levels below 12 g/dL, at the study’s start. A total of 38% had more pronounced anemia, with hemoglobin below 10 g/dL, the researchers noted.
The analysis covered 101 participants with anemia — including 52 in whom this was pronounced — who started treatment with an ESA (97%) or danazol (3%) within the first three months of the trial. The median time from enrollment to treatment was 43 days, and treatment lasted a median of 10.2 months. For comparison, the researchers used data from 1,242 participants with anemia who did not start treatment for that complication within three months.
Adding anemia meds benefits patients on Jakavi
Jakavi doses gradually decreased during treatment but remained at or higher than 25 mg daily throughout the study. Among all participants with anemia, the average dose fell from 33.4 mg during the first month to 25 mg after almost one year. A similar pattern was seen in patients with more pronounced anemia.
After three months, about 42% of participants with anemia who received treatment for anemia experienced a reduction in spleen length, and about one-quarter achieved a symptom response — meaning that overall symptoms significantly lessened — after about six months. These rates were comparable to those observed in the overall JUMP trial population and the group of participants with anemia who did not start on anemia medication within three months.
These findings indicate that “anemia-[targeting] medication … can be an early treatment option without affecting [Jakavi] clinical benefit,” the researchers wrote.
Hemoglobin levels initially declined after starting Jakavi, reaching their lowest point at one month in the overall group with anemia who received anemia-managing medications. After almost one year, mean hemoglobin levels returned to the baseline, or starting, value of 9.9 g/dL in the overall group, and increased by 6.5% in the subgroup with more severe anemia.
Patients with anemia who did not start medication to manage it within the first three months showed a similar pattern of an initial decline followed by recovery, although their hemoglobin levels reached their lowest point after two months. This means that combining anemia therapies such as ESA or danazol with Jakavi helped stabilize hemoglobin levels more quickly while allowing patients to maintain optimal drug dosing.
[Using anemia meds alongside Jakavi] provides adequate supportive care for anemia while allowing for long-term maintenance of [Jakavi] dosing.
According to the researchers, some patients’ hemoglobin levels began rising before they started anemia-targeting medication, which may have been driven in part by early blood transfusions.
The need for blood transfusions fluctuated over time, the data showed. During the first month, participants received an average of one blood transfusion over an eight-week window. This need peaked at six months, with patients receiving an average of 3.2 transfusions, before dropping back down to 1.3 transfusions by the end of one year. Of the seven patients in this subgroup who were transfusion-dependent at the start of the study, four were no longer transfusion-dependent after six months, the data showed.
These study results suggest that adding anemia-targeting medication, particularly ESAs, to Jakavi “provides adequate supportive care for anemia while allowing for long-term maintenance of [Jakavi] dosing,” the researchers wrote.
The team cautioned that the analysis was conducted after the original trial ended and involved a relatively small group of patients. Further, the review selected participants who stayed on anemia therapy for at least three months. Also, the predominant use of ESAs limited the researchers’ ability to draw conclusions about danazol.
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