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Mycophenolate efficacious and tolerable, even in elderly patients

Presented by
Dr Charlotte Bradbury, University of Bristol, United Kingdom
ASH 2020
FLIGHT is the first randomised trial using mycophenolate to treat immune thrombocytopenia (ITP), demonstrating good efficacy and tolerability, even with the inclusion of elderly patients. Mycophenolate seemed to approximately halve the risk of refractory or relapsed ITP. Therefore, mycophenolate may be considered an effective, well-tolerated first-line treatment option, alongside a short course of steroids, for some patients with ITP [1].

The currently recommended first-line ITP treatment is high-dose corticosteroids. However, this therapy is limited by frequent side effects, heterogeneous responses, and high relapse rates. One survey showed that 98% of patients experienced ≥1 side effect and 38% had to stop or reduce dose because of intolerable side effects [2]. Another problem is heterogeneity of responses using corticosteroids, with 30% of patients failing to respond at all. The majority (70–90%) of other patients will relapse at some point, while only 20% of patients remain in sustained long-term remission with this approach. In the United Kingdom, mycophenolate is a commonly used second-line treatment for ITP. Although there is no randomised controlled trial data in ITP, there is retrospective evidence suggesting that mycophenolate is effective in 50-80% of patients and is well tolerated, though responses can be delayed.

In the multicentre, open-label, randomised controlled FLIGHT trial (NCT03156452), 120 patients with ITP (27.5% were >70 years and 15.8% >75 years) requiring first-line treatment were randomised to receive corticosteroids alone (standard care) or combined corticosteroids and mycophenolate. The primary efficacy outcome was time from randomisation to treatment failure, defined as platelets <30 x 109/L and a clinical need for second-line treatment (included refractory and relapsed ITP).

Significantly fewer treatment failures occurred in patients randomised to mycophenolate (22% vs 44%; adjusted HR 0.41; P=0.0064; see Figure). With mycophenolate, significantly more patients responded and less were refractory. “Interestingly, 2 weeks after randomisation, the responses were very similar in both groups,” Dr Charlotte Bradbury (University of Bristol, United Kingdom) added. “This very much reflects the slower mechanism of action of mycophenolate.”

Figure: Proportion of patients without treatment failure in FLIGHT [1]

MMF, mycophenolate

Similar rates were observed between the groups regarding treatment side effects and bleeding events. There were no intracranial haemorrhages or fatal bleeds. Of interest, infection occurred in 14 patients in each group, whereas neutropenia occurred only in the corticosteroid-only group (n=4). No patients underwent a splenectomy during follow-up.

Patient-reported outcomes on bleeding (FACT Th6) and quality of life (ICECAP) were quite similar in both groups. Some aspects of quality of life seemed to be worse in patients assigned to the mycophenolate group, including physical role (SF36, P=0.012), mental function (SF36, P=0.519), and fatigue (FACIT-F, P=0.05).

At the final follow-up, 56% of patients treated with corticosteroids alone had not required second-line treatment, which is higher than previous reports. “So, the corticosteroid alone group did really good in this trial,” Dr Bradbury concluded. “It is unclear why some aspects of quality of life seemed to be worse in the mycophenolate group. However, it is an important reminder that disease response and patient experience may not correlate. It also emphasises the importance of including patient-reported outcomes measures within trials.”

  1. Bradbury CA, et al. A Multicentre Randomised Trial of First Line Treatment Pathways for Newly Diagnosed Immune Thrombocytopenia: Standard Steroid Treatment Versus Combined Steroid and Mycophenolate. the Flight Trial. 62nd ASH Annual Meeting, 5-8 December 2020. Abstract LBA-2.
  2. Brown TM, et al. BMC Blood Disord. 2012;12:2.

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