Initial treatment with mycophenolate mofetil plus a glucocorticoid was associated with a greater response and reduced risk of relapsed or refractory disease compared with glucocorticoid alone in patients with immune thrombocytopenia (ITP). However, the combination regimen was associated with decreased quality of life (QoL), researchers reported in a study published in the New England Journal of Medicine.
According to researchers led by Charlotte Bradbury, MBBCh, PhD, of the University of Bristol in the U.K., the recommended induction therapy for ITP is high-dose glucocorticoids, yet significant challenges associated with this treatment option include side effects, variations in response, and high rates of relapse. In the U.K., mycophenolate mofetil is widely used as a second-line therapy for ITP, although there are no head-to-head or randomized controlled trials comparing this treatment option against other regimens as a first-line therapy in the ITP patient population.
To bridge this research gap, Dr. Bradbury and colleagues designed the FLIGHT trial, which compared the combination of mycophenolate mofetil and a glucocorticoid with glucocorticoid monotherapy as initial treatment for ITP. The trial included 120 patients with ITP who were randomly assigned to either:
- glucocorticoid and mycophenolate mofetil (n=59)
- glucocorticoid alone (n=61)
Treatment failure, defined as a platelet count less than 30×109/L and use of a second-line therapy, was the primary endpoint of the study. Additional endpoints the investigators examined were response rates, side effects, bleeding, patient-reported QoL, and serious adverse events.
The mean ages of patients in the combined versus the monotherapy groups were 56.9 and 53.1 years, respectively. In the overall cohort, approximately 52.4% of patients were male. The mean platelet level was 7.9×109/L in the mycophenolate mofetil plus glucocorticoid group and 6.5×109/L in the glucocorticoid-only group. Patients were followed for up to two years following initiation of their assigned study treatment.
Patients randomly assigned to the mycophenolate mofetil combination arm experienced significantly fewer treatment failures compared with those assigned to glucocorticoid alone (22% vs. 44%, respectively; hazard ratio = 0.41; p=0.008). Initial treatment with the combination regimen was also associated with a significantly greater complete treatment response, defined as those with platelet counts greater than 100×109/L (91.5% vs. 63.9%; p<0.001).
There was no difference between the combination group and the monotherapy arm in terms of the incidence of bleeding, need for rescue treatments, or treatment side effects. Patients treated with mycophenolate mofetil, however, reported significantly worse QoL as measured by version 2 of the 36-Item Short-Form Health Survey, as well as greater fatigue as measured by version 4 of the Functional Assessment of Chronic Illness Therapy–Fatigue scale.
Based on their findings, the study investigators wrote that “mycophenolate mofetil could be used in patients for whom laboratory and clinical markers suggest that a glucocorticoid-only regimen would be expected to fail,” suggesting a place for the therapy in optimized, personalized treatment. The researchers added that early initiation of mycophenolate mofetil may also be useful for cases in which “early disease control with avoidance of relapse is a priority, either from the patient’s perspective or on clinical grounds, such as when severe bleeding or additional bleeding risk factors (e.g., the patient is receiving anticoagulation or antiplatelet therapy) are present.”
Study authors report no relevant conflicts of interest.
Reference
Bradbury CA, Pell J, Hill Q, et al. Mycophenolate mofetil for first-line treatment of immune thrombocytopenia. N Engl J Med. 2021;385(10):885-895.
