Abstract Number: OC 72.2
Meeting: ISTH 2021 Congress
Background: For most ITP patients, durable remission remains elusive and their disease becomes refractory to current treatments. Rilzabrutinib, an oral, reversible, covalent BTK inhibitor, targets mechanisms of platelet destruction. Preliminary phase I/II results in ITP showed rilzabrutinib was efficacious and safe at all dose levels, including the optimal 400 mg BID dose (NCT03395210).
Aims: Assess efficacy/safety of rilzabrutinib with longer follow-up at 400 mg BID and in long-term extension (LTE).
Methods: Eligible patients had 2 baseline platelet counts <30×109/L. Concomitant ITP therapy was permitted at stable doses. Primary endpoints: safety and ≥2 consecutive platelet counts ≥50×109/L and increased ≥20×109/L from baseline without requiring rescue medication. All patients provided informed consent.
Results: As of 09Nov2020 in 59 patients, 44 initiated rilzabrutinib 400 mg BID and to date, 14 patients with durable, stable response proceeded to LTE at 400 mg BID. For patients initiating rilzabrutinib 400 mg BID, baseline median age was 49 y, median prior therapies: 5.5 (range, 1-53; 25% prior splenectomy), and median platelet count: 16×109/L. 39% of patients initiating rilzabrutinib 400 mg BID achieved the primary endpoint at a median of 20.6 weeks (range, 1.4-24.6) on treatment (Table); 50% had platelet counts ≥30×109/L by day 8. Platelet responses to rilzabrutinib were observed irrespective of prior treatment or responses. LTE patients received rilzabrutinib for a median of 55.9 weeks (range, 13.9-84.3). All LTE patients achieved the primary endpoint response in the main treatment period and maintained platelet counts ≥50×109/L for 96% of the LTE (Figure). Treatment-related emergent adverse events were all grade 1/2, most commonly diarrhea and nausea, with no related bleeding/thrombotic events.
Conclusions: Rilzabrutinib 400 mg BID showed rapid and durable responses and was well-tolerated with longer follow-up and in LTE. This ongoing study continues to assess the magnitude and durability of clinical benefit of rilzabrutinib in ITP.
|Patients, n/n (%)||Primary Endpoint
(2 Consecutive Platelet Counts
|50% of Platelet
|8 of Final 12 Week
Platelet Counts ≥50×109/L
|Initiated 400 mg BID||17/44 (39)||14/44 (32)||12/44 (27)|
|8/14 (57)||6/14 (43)||5/14 (36)|
|Prior therapy||Responded||No Response|
|BID, twice daily; ITP, immune thrombocytopenia; TPO-RA, thrombopoietin receptor agonists.|
To cite this abstract in AMA style:Kuter DJ, Tzvetkov N, Efraim M, Kaplan Z, Mayer J, Choi P, Jansen AJG, McDonald V, Baker R, Bird R, Garg M, Gumulec J, Kostal M, Gernsheimer T, Ghanima W, Bandman O, Arora P, Tran Q, Guo H, Cooper N. Phase I/II Ongoing Study of Rilzabrutinib, an Oral Bruton Tyrosine Kinase Inhibitor, in Immune Thrombocytopenia: Extended Follow-up and Long-term Analyses with Optimal Dose [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/phase-i-ii-ongoing-study-of-rilzabrutinib-an-oral-bruton-tyrosine-kinase-inhibitor-in-immune-thrombocytopenia-extended-follow-up-and-long-term-analyses-with-optimal-dose/. Accessed December 6, 2023.
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