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Professor of Medicine
Massachusetts General Hospital Cancer Center
Harvard Medical School
Hematology Program Director
Massachusetts General Hospital Cancer Center
Massachusetts General Hospital
David J. Kuter, MD, DPhil, has disclosed that he has received funds for research support from Actelion (Syntimmune), Agios, Alnylam, Amgen, Argenx, Bristol-Myers Squibb, Immunovant, Kezar, Principia, Protalex, Rigel, Takeda (Bioverativ), and consulting fees from Actelion (Syntimmune), Agios, Alnylam, Amgen, Argenx, Bristol-Myers Squibb, Caremark, CRICO, Daiichi Sankyo, Dova, Genzyme, Immunovant, Incyte, Kyowa-Kirin, Merck Sharp & Dohme, Momenta, Novartis, Pfizer, Platelet Disorder Support Association, Principia, Protalex, Protalix, Rigel, Sanofi, Genzyme, Shionogi, Shire, Takeda (Bioverativ), UCB, and Zafgen.
Immune thrombocytopenia (ITP) is characterized by immune-mediated platelet destruction and impairment of platelet production, an increased likelihood of bleeding, and decreased quality of life. In this commentary, I preview key ITP abstracts to be presented at the 2020 ASH meeting. As the ASH annual meeting unfolds, remember to check the CCO Web site often for downloadable slidesets summarizing the data from these and other studies and CME-certified online activities featuring expert commentaries on the clinical implications of the data.
First-line Treatment Strategies
Standard first-line therapy for ITP includes high-dose corticosteroids, but prolonged exposure to these agents can be associated with significant toxicities. In addition, most patients will not achieve long-term remission with corticosteroids alone, suggesting more effective strategies are needed. At the 2020 ASH meeting, we will see results from a randomized trial in which 120 patients with ITP who required first-line treatment received either corticosteroids alone or combination therapy with corticosteroids plus mycophenolate, an agent that is frequently used as second-line therapy for ITP. This will be the first randomized trial of mycophenolate for patients with ITP, and the abstract suggests encouraging efficacy results with this combination.
Optimizing Second-line Therapy
For patients who require second-line therapy following corticosteroids, several novel agents are now approved by the FDA and may be considered in specific scenarios, including the thrombopoietin (TPO) receptor agonists avatrombopag, eltrombopag, and romiplostim, and the Syk inhibitor fostamatinib. At the 2020 ASH meeting, we will see data from several studies of these agents.
The most recent TPO receptor agonist to be approved by the FDA for ITP is avatrombopag, which has been available since June 2019. As a class, TPO receptor agonists potentiate endogenous platelet production, and this can increase the risk of thromboembolism. To characterize the thromboembolic events in the avatrombopag ITP clinical development program, Piatek and colleagues assessed results from 2 phase II and 2 phase III trials in which a total of 128 patients received avatrombopag; they will present their findings at ASH 2020. Factors recorded at the time of each thromboembolic event included platelet count, avatrombopag dose, study day of event, and other medical and lifestyle factors that could increase the risk of thromboembolism.
Eltrombopag has been available for the treatment of ITP for more than 10 years, with the indication expanded in 2019 to include patients with primary ITP lasting 6 months or longer from diagnosis and who are refractory to other treatments. At ASH 2020, Moulis and colleagues will present real-world efficacy and safety data for eltrombopag from the Elextra study, in which newly diagnosed adults with ITP from the CARMEN-France registry were assessed (N = 795). This study should provide interesting data on the use of eltrombopag in clinical practice.
An ongoing question in the field is whether or not patients with primary ITP who are receiving TPO receptor agonists should remain on treatment indefinitely to maintain platelet production. Case reports and cohort studies have suggested that some patients with ITP may be able to discontinue TPO receptor agonists after some period of treatment and maintain a hemostatic platelet count. At ASH 2020, clinical recommendations from a panel of experts will be presented regarding when and how to taper TPO receptor agonists in children and adults with persistent or chronic primary ITP. The expert panel included 9 hematologists (with an average of 25 years of experience) and 1 patient representative. The panel was provided with evidence summaries from 12 case reports, 11 cohort studies, and 2 clinical trial analyses of sustained remissions. Panel recommendations are intended to guide clinical practice and inform the design of clinical trials that will prospectively test the safety of tapering TPO receptor agonists in patients with ITP.
Emerging Strategies for Patients With Refractory ITP
Numerous novel investigational agents are currently being assessed for treating patients with ITP. At the 2020 ASH meeting, we will see data on the emerging therapeutics sutimlimab and rilzabrutinib.
A subset of patients with ITP have persistent thrombocytopenia due to complement pathway activation. Sutimlimab is an investigational monoclonal antibody that targets and inhibits the classical complement pathway component C1s. Broome and colleagues will present updated long-term results from an ongoing open-label phase I trial of sutimlimab in patients with multirefractory chronic ITP (N = 12). The primary study endpoints include safety, pharmacokinetics/pharmacodynamics, and durable platelet response.
Rilzabrutinib is an investigational BTK inhibitor that has been shown to inhibit platelet destruction but not platelet aggregation. At ASH 2020, I will present results from an open-label phase I/II study of rilzabrutinib for heavily pretreated patients with relapsed ITP and platelet counts < 30 x 109/L (N = 32). The primary endpoint of this study was at least 2 consecutive platelet counts ≥ 50 x 109/L and an increase of ≥ 20 x 109/L from baseline without rescue medication.
What ITP studies are you most interested in at the 2020 ASH meeting? Please answer the polling question on your screen and share your thoughts in the comments box.