Rilzabrutinib for persistent or chronic immune thrombocytopenia (ITP): a Bruton tyrosine kinase inhibitor that can target multiple pathophysiological pathways

Immune Thrombocytopenia during Childhood: New Approaches to Classification and Management

LUNA3 Phase III Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of the Oral BTK Inhibitor Rilzabrutinib in Adults and Adolescents with Persistent or Chronic Immune Thrombocytopenia

Hetrombopag for patients with persistent primary immune thrombocytopenia: A post-hoc analysis of a multicenter, randomized phase Ⅲ Trial

Immune thrombocytopenia (ITP) is a chronic autoimmune disorder associated with platelet destruction and increased bleeding risk, substantial economic burden, and impairment of health-related quality of life. The pathophysiology of ITP involves increased platelet destruction and impaired platelet production due to a multifactorial breakdown of immune tolerance driven by dysregulated B and T cells. Advances in understanding ITP pathophysiology have led to the development of new immune-modulating therapies, such as Bruton tyrosine kinase (BTK) inhibitors. Rilzabrutinib (Wayrilz; Sanofi) is an oral BTK inhibitor recently approved for treatment of adult patients with persistent or chronic ITP who have had an insufficient response to a previous treatment. Rilzabrutinib targets several aspects of ITP disease pathophysiology by modulating multiple immune pathways. Approval was based on results from a phase 3 trial (LUNA 3 [NCT04562766]), in which patients with ITP who received rilzabrutinib demonstrated a rapid, durable platelet response and improvements in fatigue and bleeding with a tolerable safety profile.

Enhanced Responses to Fostamatinib As Second-Line Therapy and in Persistent Immune Thrombocytopenia (ITP) Patients

Romiplostim for the Treatment of Adult Patients with Newly Diagnosed or Persistent Immune Thrombocytopenia: Subgroup Analysis from a Phase 2 Study

French Observatory of Adult' Chronic Immune Thrombocytopenia (ITP) Treated By Thrombopoietin Receptor Agonists (TPO-RAs)

Clinical Burden of Illness in Patients with Persistent or Chronic Primary Immune Thrombocytopenia Treated with Advanced Therapies in the United States

The purpose of this research is to study the outcomes of splenectomy for chronic and persistent immune thrombocytopenia (ITP). This study is a retrospective analysis of 254 patients with chronic or persistent ITP who underwent splenectomy at CMC, Vellore, India between 1995 and 2009. Responses were assessed based on standard criteria. One hundred and sixty seven adults and 87 children with a median age of 29years (range 2-64) with persistent (n = 103) or chronic ITP (n = 151) was studied. Response was seen in 229 (90.2%) including CR in 74.4% at a median time of 1day (range 1-54). Infections following splenectomy were reported in 16%. Deaths related to post splenectomy sepsis occurred in 1.57% and major bleeding in 0.78%. At median follow-up of 54.3months (range 1-290), 178 (70.1%) remain in remission. The 5-year and 10-year overall survival (OS) is 97.4 ± 1.2% and 94.9 ± 2.1%, respectively, while the 5-year and 10-year event-free survival (EFS) is 76.5 + 2.9% and 71.0 + 3.9%, respectively. Splenectomy is associated with long-term remission rates of >70% in chronic or persistent ITP.

Objective To discuss DNA methylation's effect on pathogenesis of pediatric immune thrombocytopenia (ITP)through detecting the expression level of DNA methyltransferases (DNMTs)mRNA in peripheral blood lymphocytes of children with ITP. Methods Two mL peripheral blood was collected from each of 25 children with persistent and chronic ITP and 20 healthy children(the healthy control group)by using aseptic method in the pediatric ward of the First Affiliated Hospital of Xinxiang Medical University from January 2014 to January 2015.First ethylenediamine tetraacetic acid (EDTA) was used as the anticoagulant.Then separate the mononuclear cells, extract RNA and detect expression levels of DNMT1, DNMT3A and DNMT3B mRNA using reverse transcription-polymerase chain reaction (RT-PCR) method. Results (1)The blood platelet(PLT) of children with persistent and chronic ITP was (36.2±19.6)×109/L, which was obviously lower than the healthy control group(168.8±46.8)×109/L(t=-11.85, P=0.000). (2)The DNMT1 mRNA expression level of children with persistent and chronic ITP was 0.17±0.05, which was obviously lower than the healthy control group (0.27±0.10) (t=-3.912, P=0.001). The DNMT3A mRNA expression level of children with persistent and chronic ITP was 0.20±0.10, which was obviously lower than the healthy control group (0.32±0.11) (t=-3.779, P=0.000). The DNMT3B mRNA expression level of children with persistent and chronic ITP was 0.16±0.11, which was obviously lower than the healthy control group (0.31±0.11) (t=-4.641, P=0.000). (3) There was positive correlation between the expression of DNMT1 and DNMT3B mRNA(r=0.433, P=0.031). There was positive correlation between the expression of DNMT3A and DNMT3B mRNA(r=0.721, P=0.000). Conclusions (1) Children with persistent and chronic ITP have lower expression levels of DNMT1, DNMT3A, DNMT3B mRNA, which indicates that DNA methylation contributes to the pathogenesis of pediatric persistent and chronic ITP.(2) DNMTs have synergistic effect on DNA methylation of pediatric persistent and chronic ITP. Key words: Child; Immune thrombocytopenia, persistent, chronic; DNA methyltransferase

A Prospective Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of Lusutrombopag in Chinese Adults with Persistent or Chronic Primary Immune Thrombocytopenia

Treatment Patterns Among Patients with Immune Thrombocytopenia (ITP) in the United States: An Electronic Medical Record (EMR)-Based Analysis

Comparison of the Effects of the Thrombopoietin (TPO) Receptor Agonist Romiplostim in Patients with Immune Thrombocytopenia (ITP) for ≤1 Year Vs. >1 Year

Central nervous system lymphoma (CNSL) is aggressive, and treatment with Bruton tyrosine kinase (BTK) inhibitors (BTKis) plays a key role. For this systematic review and meta-analysis, the authors evaluated BTKis for the treatment of primary CNSL (PCNSL) and secondary CNSL (SCNSL). By May 1, 2025, the authors conducted a systematic search of databases, including PubMed, EMBASE, etc. Included studies were those that investigated BTKi-treated CNSL and analyzed the overall response rate (ORR) as well as the complete response (CR) and partial response (PR) rates using systematic review and meta-analysis software. Forty studies (935 patients) were included in the meta-analysis. The pooled ORR and CR and PR rates were 73%, 49%, and 28%, respectively. The pooled ORR and CR rates for BTKi monotherapy were 60% and 34%, respectively; whereas the rates for BTKi plus chemotherapy or immunochemotherapy were 79% and 55%, respectively. For PCNSL, the pooled ORR and PR rates were 73% and 49%, respectively. For SCNSL, the pooled ORR and CR rates reached 75% and 53%, respectively. Among patients with PCNSL, zanubrutinib achieved pooled ORR and CR rates of 85% and 54%, respectively. Ibrutinib had pooled ORR and CR rates of 67% and 46%, respectively; whereas orelabrutinib demonstrated pooled ORR and CR rates of 70% and 59%, respectively. For SCNSL, zanubrutinib achieved pooled ORR and CR rates of 77% and 62%, respectively; whereas ibrutinib achieved rates of 72% and 54%, respectively. Hematologic toxicities and transaminase increases were grade 3-5 toxicities according to common toxicity criteria. The combination of BTKis with traditional chemotherapy or immunochemotherapy offers superior response rates compared with BTKis alone, and the safety profile is acceptable. Efficacy varies by BTKi type and should be selected based on patient condition. Specifically, for PCNSL, the response rates of zanubrutinib and obinutuzumab are better; for SCNSL, there is a minimal difference in efficacy among the various BTKis; and, overall, regardless of whether it is PCNSL or SCNSL, the off-target effects and side effects of covalent BTKis (zanubrutinib, obinutuzumab), except for ibrutinib, have improved.

Loxo-305, a Highly Selective and Non-Covalent Next Generation BTK Inhibitor, Inhibits Diverse BTK C481 Substitution Mutations