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Immune thrombocytopenia (ITP) is an autoimmune disease associated with autoantibody-mediated platelet destruction and impaired platelet production, resulting in thrombocytopenia and a predisposition to bleeding. The ongoing, global phase 1/2 study showed that rilzabrutinib, a Bruton tyrosine kinase inhibitor specifically developed to treat autoimmune disorders, could be an efficacious and well-tolerated treatment for ITP. Clinical activity, durability of response, and safety were evaluated in 16 responding patients who continued rilzabrutinib 400 mg twice daily in the long-term extension (LTE) study. At LTE entry, the median platelet count was 87 × 109/L in all patients, 68 × 109/L in those who had rilzabrutinib monotherapy (n = 5), and 156 × 109/L in patients who received concomitant ITP medication (thrombopoietin-receptor agonists and/or corticosteroids, n = 11). At a median duration of treatment of 478 days (range, 303-764), 11 of 16 patients (69%) continued to receive rilzabrutinib. A platelet count of ≥50 × 109/L was reported in 93% of patients for more than half of their monthly visits. The median percentage of LTE weeks with platelet counts ≥30 × 109/L and ≥50 × 109/L was 100% and 88%, respectively. Five patients discontinued concomitant ITP therapy and maintained median platelet counts of 106 × 109/L at 3 to 6 months after stopping concomitant ITP therapy. Adverse events related to treatment were grade 1 or 2 and transient, with no bleeding, thrombotic, or serious adverse events. With continued rilzabrutinib treatment in the LTE, platelet responses were durable and stable over time with no new safety signals. This trial is registered at www.clinicaltrials.gov as #NCT03395210 and www.clinicaltrialsregister.eu as EudraCT 2017-004012-19.

MeSH
idiopatická trombocytopenická purpura * farmakoterapie chemicky indukované MeSH
krvácení chemicky indukované MeSH
lidé MeSH
receptory Fc MeSH
thrombopoetin terapeutické užití MeSH
trombocytopenie * chemicky indukované MeSH
výsledek terapie MeSH
Check Tag
lidé MeSH
Publikační typ
časopisecké články MeSH
klinické zkoušky, fáze I MeSH
klinické zkoušky, fáze II MeSH

Článek

Lymphocyte subpopulations: a potential predictor of a response in patients with immune thrombocytopenia

Hematology. 2024 ; 29 (1) : 2304486. [pub] 20240122

ISSN 1607-8454
Medvik
Zdroj

OBJECTIVES: Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder caused by increased platelet destruction and altered production. Despite the well-described pathophysiological background of immune dysregulation, current treatment guidelines consist of monotherapy with different drugs, with no tool to predict which patient is more suitable for each therapeutic modality. METHODS: In our study, we attempted to determine differences in the immune setting, comparing the patients' responses to administered therapy. During 12-month follow-up, we assessed blood count, antiplatelet autoantibodies, and T lymphocyte subsets in peripheral blood in 35 patients with ITP (newly diagnosed or relapsed disease). RESULTS: Our data show that the value of antiplatelet autoantibodies, the percentage of cytotoxic T lymphocytes, and the immunoregulatory index (IRI, CD4+ / CD8+ T cell ratio) differ significantly by treatment response. Responders have a higher IRI (median 2.1 vs. 1.5 in non-responders, P = 0.04), higher antiplatelet autoantibodies (median 58 vs. 20% in non-responders, P = 0.01) and lower relative CD8+ T cells count (P = 0.02) before treatment. DISCUSSION: The results suggest that immunological parameters (antiplatelet autoantibodies, relative CD8+ T cell count and IRI) could be used as prognostic tools for a worse clinical outcome in patients with ITP. CONCLUSION: These biomarkers could be utilized for stratification and eventually selection of treatment preferring combination therapy.