Adding Mycophenolate to Corticosteroids Improves Response as Frontline ​Option in Immune Thrombocytopenia

In results from the randomized, controlled FLIGHT trial, patients with immune thrombocytopenia (ITP) who received mycophenolate mofetil (MMF) plus corticosteroids as first-line therapy were more likely to respond to treatment, compared with those who received corticosteroids alone. Charlotte Bradbury, MBBCh, PhD, from the University of Bristol in the U.K., presented these findings as a late-breaking abstract at the 2020 ASH Annual Meeting.

“The current standard of care of corticosteroids alone [for initial treatment of ITP] has many downsides,” Dr. Bradbury told ASH Clinical News. “Not only do most patients have side effects from steroids, but also there is a heterogeneity of responses, with some patients – about 30% – not responding at all. Most patients will relapse in the future, which means only about 20% stay well long-term with this approach.”

MMF is frequently used in the U.K. as second-line treatment, she added, with retrospective data suggesting an efficacy rate of 50% to 80% of patients with good tolerability. In the FLIGHT trial, investigators evaluated whether combining MMF with standard first-line treatment could improve responses.

The primary efficacy outcome was time from randomization to treatment failure (defined as platelets <30×109/L and a clinical need for second-line treatment). Secondary outcomes included adverse events (AEs), bleeding events, and patient reported outcomes measures (PROMs) from baseline to 12 months.

Patients with ITP (baseline platelet count <30×109/L) were randomized 1:1 to receive corticosteroids alone (n=61) or a combination of corticosteroids and MMF (n=59). Patient characteristics were similar between the two groups, Dr. Bradbury noted. Among the 120 participants, the mean baseline platelet count was 7×109/L and the mean follow-up was 18 months (range = 12-24).

During study follow-up, significantly fewer treatment failures occurred in patients randomized to receive MMF, compared with corticosteroids alone: 22% versus 44% (adjusted hazard ratio [aHR] = 0.41; p=0.0064).

Dr. Bradbury added that participants who received MMF also had higher rates of partial or complete response, and fewer patients had refractory disease (6.8% vs. 24.6%). Response rates were similar between the two groups during the first 2 weeks of study, which, she said, “reflects the slower mechanism of action of mycophenolate.”

Rates of AEs were also similar between the two treatment arms, and the most commonly reported side effects were typical effects of corticosteroids. These included weight gain (29% for MMF vs. 34% for standard of care), difficulty sleeping (36% vs. 28%), and mood change (31% vs. 34%). The investigators noted that incidence of severe AEs, bleeding events, use of rescue treatments, and hospital admissions were comparable, as well. “Thankfully, there were no intracranial hemorrhages or fatal bleeds, and no patients underwent a splenectomy during follow-up,” Dr. Bradbury said.

When looking at PROMs, though, some aspects of quality of life were worse in those patients assigned to the MMF group than those assigned to receive corticosteroids alone. These included higher scores of fatigue and impaired physical functioning on PROM surveys.

“[These results] show, we think, very good efficacy and surprising tolerability, considering the inclusion of so many elderly patients, with 27.5% over 70 years and 15.8% over 75 years,” Dr. Bradbury concluded. Given that the combination also seemed to approximately halve the risk of being failed by therapy, she added, “MMF may be considered first-line alongside a short course of corticosteroids in some patients with ITP.”

The authors report no relevant conflicts of interest.


Bradbury CA, Greenwood R, Pell J, et al. A multicentre randomised trial of first line treatment pathways for newly diagnosed immune thrombocytopenia: standard steroid treatment versus combined steroid and mycophenolate. Abstract LBA-2. Presented at the 2020 American Society of Hematology Annual Meeting, December 8, 2020.