Abstract Introduction Immune thrombocytopenia (ITP) is characterized by immune dysregulation leading to platelet destruction and impaired platelet production causing thrombocytopenia, increased bleeding risk, and diminished quality of life. Corticosteroids (CS) are often used in front-line, concomitant, and rescue therapy for patients (pts) with ITP; however, long-term or repeated CS use is associated with elevated toxicity. Rilzabrutinib is an oral, reversible, covalent, selective Bruton tyrosine kinase inhibitor that acts through multi-immune modulation. The phase 3 LUNA3 study (NCT04562766, 2020-002063-60) of rilzabrutinib in adult pts with persistent/chronic ITP comprised 3 phases: double-blind (DB), open label (OL), and long-term extension (LTE). Rilzabrutinib demonstrated rapid and durable platelet response; improved physical fatigue and bleeding scores; and favorable safety profile in the DB, OL, and interim analysis of the LTE periods. Reported here are updated results based on longer follow-up from the LUNA3 LTE period, with a special focus on changes in concomitant use of CS from baseline. Methods Pts eligible to enter the LTE had response (platelet count ≥50×109/L or ≥30x109/L and at least doubled from baseline at ≥50% of visits without rescue therapy) during the last 8 weeks of the OL period. In the LTE, pts received oral rilzabrutinib 400 mg bid until loss of response on 2 consecutive visits or for safety reasons. Stable baseline doses of concomitant CS and/or thrombopoietin-receptor agonists (TPO-RA), dose reduction/discontinuation, and rescue therapy were allowed. Results As of April 1, 2025, 69 of 202 (34%) pts who met the predefined response criteria had entered LTE (48 rilzabrutinib pts from DB, including 25 durable platelet responders and 23 non-responders; 21 non-responding placebo pts from DB), and 57 were ongoing in the LTE (41 rilzabrutinib pts, including 23 responders and 18 non-responders from DB; 16 placebo pts from DB). Forty-three (62%) pts had completed ≥12 mo of follow-up in LTE. At baseline, median age of LTE pts was 52 years (range, 18-80), 72% were female. Median duration of ITP was 9.6 years (range, 0.3-42.7), median number of unique prior therapies was 4 (range, 1-9; 26% splenectomized), and 97% of pts had received CS; median baseline platelet count was 18×109/L (range, 2-54×109/L). Median platelet count at LTE entry was 113×109/L (range, 20-877×109/L) and median counts at LTE follow-up visits ranged from 83-168×109/L through 33 mo of LTE. During the first 12 mo of the LTE, pts had platelet counts ≥50×109/L or between 30-50×109/L and at least doubled from baseline for an average of 88% (SD, 24%) of visits. Of pts who received rilzabrutinib monotherapy (n=22, 32%) or rilzabrutinib and concomitant CS and/or TPO-RA (n=47, 68%), median platelet counts at LTE entry were 78×109/L (range, 20-371×109/L) and 115×109/L (range, 28-877×109/L), respectively, and ranged from 78-270×109/L and 90-160×109/L, respectively, through 33 mo of LTE. In the LTE, 14 (20%) pts received rescue medication. Among 34 (49%) pts who entered the LTE on concomitant CS, 10 (29%) discontinued CS use (switched to rilzabrutinib monotherapy), 2 (6%) reduced their CS ≥50% from DB baseline, and 6 (18%) reduced their CS dose to 5 mg (prednisone qd). Median platelet counts before and after CS discontinuation at last available LTE visit were 148×109/L (range, 19-722×109/L) and 178×109/L (range, 3-405×109/L), respectively. Improvements in fatigue scores (ITP-PAQ Item 10) and bleeding symptoms (IBLS) were generally maintained during the LTE. Thirteen (19%) pts had treatment-emergent adverse events (TEAE) that were assessed as related by the investigator; most common were nausea (7%), diarrhea (4%), and upper abdominal pain (3%). Two pts (3%) had grade ≥2 related TEAE of infection; no related grade ≥2 bleeding events, serious adverse events, or deaths occurred. Conclusion Rilzabrutinib continued to demonstrate sustained platelet responses and improvement in all ITP-related symptoms in pts with ITP during the LTE period. Most pts receiving concomitant CS were able to taper or discontinue CS while maintaining platelet responses. Rilzabrutinib continued to demonstrate favorable safety profile in pts with ITP. These LTE findings support rilzabrutinib as an efficacious therapy with durable therapeutic effects and steroid-sparing potential, and underscores further the disease-modifying potential of multi-immune modulation in pts with ITP.
Ghanima et al. (Mon,) studied this question.