preheader BJH 1

Rapid and durable responses with rilzabrutinib in the treatment of immune thrombocytopenia

Despite recent therapeutic advances, durable remissions remain an unmet need for relapsed/refractory immune thrombocytopenia (ITP) patients. The Bruton’s tyrosine kinase inhibitor (BTKi) rilzabrutinib now demonstrated rapid and durable responses, with half of the patients achieving platelet counts ≥30×109/L by day eight. In addition, rilzabrutinib was well tolerated, without any treatment-related thrombotic events or an increased bleeding risk.

Immune thrombocytopenia (ITP) is characterised by immune-mediated platelet destruction and an impaired platelet production, triggering thrombocytopenia, and a predisposition for bleeding. Rilzabrutinib is an oral, reversible, covalent inhibitor of Bruton’s tyrosine kinase (BTK) that targets immune-mediated ITP activities and simultaneously has rapid anti-inflammatory effects.

Rilzabrutinib in the treatment of ITP

At EHA 2021, Prof. Kuter presented the results of an adaptive, open-label, dose-finding, phase I/II study of oral rilzabrutinib in relapsed/refractory ITP. Enrolled patients (N= 59) were 18-80 years old and, experienced a response to at least one prior ITP therapy and had no other available or approved treatment options left. Patients had to have at least two platelet counts below 30x109/L at study entry. Finally, stable concomitant corticosteroid and/or thrombopoietin receptor agonists were allowed. In the 24-week phase I/II intrapatient dose escalation study, patients started at various dosing of rilzabrutinib (200 mg QD, 400 mg QD, 300 mg BID and 400 mg BID), but the vast majority (N= 44) received 400 mg BID. The primary endpoints are safety and ≥2 consecutive platelet counts ≥50×109/L (increased ≥20×109/L from baseline) without requiring rescue medication. Patients who responded well to treatment could enter a long-term extension study (LTE) with oral rilzabrutinib at 400 mg BID. Overall, 27 patients completed the 24-week treatment period and 14 patients entered the LTE.

Study results

Patients included in the trial were heavily pretreated, with a median of six prior therapies. All patients had received at least one prior ITP treatment and the median duration of ITP was more than six years. A total of 23 patients (39%) overall and 17 patients (39%) initiating 400 mg BID achieved the primary efficacy endpoint. Primary responses were observed irrespective of prior treatments or responses. Furthermore, responses were maintained for the duration of the 24-week period for 75% of weeks at ≥50×109/L and 87% of weeks at ≥20×109/L above baseline. Platelet responses also had a fast onset; by day eight, approximately 50% of patients in both groups achieved platelet counts ≥30×109/L. Day 8 platelet count was associated with a high negative predictive value for achieving the primary endpoint (>80%) and could be used to identify patients unlikely to reach the targeted primary platelet response. Throughout the 24-week treatment period, median platelet counts remained elevated in patients who had platelet counts ≥50×109/L by day 8 (early responders) or any time (late responders) compared with non-responders. The median treatment duration period was 20.1 weeks for all patients and 20.6 weeks for patients receiving 400 mg BID. Treatment-related adverse events (TRAEs) were all of grade 1 or 2, were transient in nature and were observed in 28 out of 59 patients. Three patients discontinued rilzabrutinib due to TRAEs. The most commonly observed TRAEs were diarrhoea (30%), nausea (26%), fatigue (9%), abdominal distention (7%) and abdominal pain (3%). There were no related bleeding/thrombotic events, ECG abnormalities, hypertension, or liver enzyme elevations.


This is the first clinical trial to establish the role of BTK inhibition in ITP treatment. Both in the overall population and in the subgroup of patients starting rilzabrutinib at a dose of 400 mg BID, 39% of patients achieved the primary endpoint platelet response. Responding patients showed rapid and durable responses. Oral rilzabrutinib was well tolerated, with no related thrombotic events and no increase in bleeding. Currently enrolling ITP trials will further demonstrate the magnitude and durability of rilzabrutinib’s clinical benefit.


Kuter D, Tzvetkov N, Efraim M, et al. Phase I/II updated safety and efficacy results of oral bruton tyrosine kinase (BTK) inhibitor rilzabrutinib in relapsed/refractory immune thrombocytopenia (ITP). Presented at EHA 2021; abstract S299.

Speaker David Kuter

David Kuter

David Kuter, MD, PhD, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States


See: Keyslides


Back to Top