Rilzabrutinib for the Treatment of Immune Thrombocytopenia

被引:0
作者
Labanca, Caterina [1 ]
Martino, Enrica Antonia [1 ]
Vigna, Ernesto [1 ]
Bruzzese, Antonella [1 ]
Mendicino, Francesco [1 ]
Carida, Giulio [1 ]
Lucia, Eugenio [1 ]
Olivito, Virginia [1 ]
Manicardi, Veronica [2 ]
Amodio, Nicola [3 ]
Neri, Antonino [4 ]
Morabito, Fortunato [5 ]
Gentile, Massimo [1 ,6 ]
机构
[1] Azienda Osped Annunziata, Hematol Unit, Cosenza, Italy
[2] Azienda USL IRCSS Reggio Emilia, Lab Ric Traslazionale, Reggio Emilia, Italy
[3] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Catanzaro, Italy
[4] IRCCS Reggio Emilia, Sci Directorate, Reggio Emilia, Italy
[5] Grp Amici Ematol Fdn GrADE, Radiol Unit, Reggio Emilia, Italy
[6] Univ Calabria, Dept Pharm Hlth & Nutr Sci, Arcavacata Di Rende, Italy
关键词
Bruton's tyrosine kinase inhibitor; platelet response; refractory immune thrombocytopenia; rilzabrutinib; BRUTONS TYROSINE KINASE; QUALITY-OF-LIFE; COMPLEMENT ACTIVATION; IMMATURE PLATELETS; ADULT PATIENTS; PURPURA ITP; BTK; INHIBITOR; RECEPTOR; PHOSPHORYLATION;
D O I
10.1111/ejh.14425
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Advancements in the understanding of ITP pathogenesis have led to significant improvements in disease management through the use of both traditional immunosuppressive strategies and novel targeted therapies. However, a subset of patients remains refractory to treatment or achieves only transient benefits, underscoring the need for alternative therapeutic approaches. Bruton's tyrosine kinase (BTK) inhibitors have emerged as a promising strategy for autoimmune cytopenias, including ITP, due to their ability to modulate key immune pathways. Rilzabrutinib, an oral, reversible BTK inhibitor, represents a novel therapeutic approach for ITP. Rilzabrutinib, an oral, reversible BTK inhibitor, offers a novel mechanism of action by preserving platelet aggregation while reducing macrophage-mediated platelet clearance, distinguishing it from irreversible BTK inhibitors. This review provides an updated and comprehensive analysis of the Phase 1/2 LUNA 2 trial and its long-term extension, contextualizing rilzabrutinib within the broader treatment landscape. We also offer a comparative assessment of other BTK inhibitors investigated for ITP and discuss rilzabrutinib's potential positioning relative to existing therapies, including thrombopoietin receptor agonists (TPO-RAs), rituximab, fostamatinib, and immunosuppressants. Results from the phase 1/2 LUNA 2 trial and its long-term extension demonstrated that Rilzabrutinib induced a durable platelet response in 40% of patients, with a median time to response of 11.5 days. The treatment exhibited a favorable safety profile, with predominantly grade 1 or 2 adverse events and no significant safety concerns commonly associated with BTK inhibitors, such as increased bleeding risk, hepatic toxicity, or cardiac arrhythmias. Preliminary data presented at ASH 2024 from the ongoing Phase 3 LUNA 3 trial, a randomized, double-blind study, further support rilzabrutinib's efficacy and long-term safety. If confirmed, these findings suggest that rilzabrutinib could represent a valuable therapeutic option for patients with refractory ITP, addressing a critical unmet need and potentially redefining treatment paradigms.
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收藏
页码:4 / 15
页数:12
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