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@article{1863066,
author = {Kuter, D. J. and Efraim, M. and Mayer, Jiří and Trněný, Marek and McDonald, V. and Bird, R. and Regenbogen, T. and Garg, M. and Kaplan, Z. and Tzvetkov, N. and Choi, P. Y. and Jansen, A. J. G. and Kostal, Milan and Baker, R. and Gumulec, Jaromir and Lee, E. J. and Cunningham, I. and Goncalves, I. and Warner, M. and Boccia, R. and Gernsheimer, T. and Ghanima, W. and Bandman, O. and Burns, R. and Neale, A. and Thomas, D. and Arora, P. and Zheng, B. and Rilzabrutinib, Cooper N.},
article_location = {Waltham},
article_number = {15},
doi = {http://dx.doi.org/10.1056/NEJMoa2110297},
keywords = {Rilzabrutinib; Oral BTK Inhibito; Immune Thrombocytopenia},
language = {eng},
issn = {0028-4793},
journal = {New England Journal of Medicine},
title = {Rilzabrutinib, an Oral BTK Inhibitor, in Immune Thrombocytopenia},
url = {https://www.nejm.org/doi/10.1056/NEJMoa2110297},
volume = {386},
year = {2022}
}
TY - JOUR
ID - 1863066
AU - Kuter, D. J. - Efraim, M. - Mayer, Jiří - Trněný, Marek - McDonald, V. - Bird, R. - Regenbogen, T. - Garg, M. - Kaplan, Z. - Tzvetkov, N. - Choi, P. Y. - Jansen, A. J. G. - Kostal, Milan - Baker, R. - Gumulec, Jaromir - Lee, E. J. - Cunningham, I. - Goncalves, I. - Warner, M. - Boccia, R. - Gernsheimer, T. - Ghanima, W. - Bandman, O. - Burns, R. - Neale, A. - Thomas, D. - Arora, P. - Zheng, B. - Rilzabrutinib, Cooper N.
PY - 2022
TI - Rilzabrutinib, an Oral BTK Inhibitor, in Immune Thrombocytopenia
JF - New England Journal of Medicine
VL - 386
IS - 15
SP - 1421-1431
EP - 1421-1431
PB - Massachussetts Medical Society
SN - 00284793
KW - Rilzabrutinib
KW - Oral BTK Inhibito
KW - Immune Thrombocytopenia
UR - https://www.nejm.org/doi/10.1056/NEJMoa2110297
N2 - BACKGROUND & nbsp;Rilzabrutinib, an oral, reversible covalent inhibitor of Bruton's tyrosine kinase, may increase platelet counts in patients with immune thrombocytopenia by means of dual mechanisms of action: decreased macrophage (Fc gamma receptor)-mediated platelet destruction and reduced production of pathogenic autoantibodies.& nbsp;METHODS & nbsp;In an international, adaptive, open-label, dose-finding, phase 1-2 clinical trial, we evaluated rilzabrutinib therapy in previously treated patients with immune thrombocytopenia. We used intrapatient dose escalation of oral rilzabrutinib over a period of 24 weeks; the lowest starting dose was 200 mg once daily, with higher starting doses of 400 mg once daily, 300 mg twice daily, and 400 mg twice daily. The primary end points were safety and platelet response (defined as at least two consecutive platelet counts of >= 50x10(3) per cubic millimeter and an increase from baseline of >= 20x10(3) per cubic millimeter without the use of rescue medication).& nbsp;RESULTS & nbsp;Sixty patients were enrolled. At baseline, the median platelet count was 15x10(3) per cubic millimeter, the median duration of disease was 6.3 years, and patients had received a median of four different immune thrombocytopenia therapies previously. All the treatment-related adverse events were of grade 1 or 2 and transient. There were no treatment-related bleeding or thrombotic events of grade 2 or higher. At a median of 167.5 days (range, 4 to 293) of treatment, 24 of 60 patients (40%) overall and 18 of the 45 patients (40%) who had started rilzabrutinib treatment at the highest dose met the primary end point of platelet response. The median time to the first platelet count of at least 50x10(3) per cubic millimeter was 11.5 days. Among patients with a primary platelet response, the mean percentage of weeks with a platelet count of at least 50x10(3) per cubic millimeter was 65%.& nbsp;CONCLUSIONS & nbsp;Rilzabrutinib was active and associated with only low-level toxic effects at all dose levels. The dose of 400 mg twice daily was identified as the dose for further testing. Overall, rilzabrutinib showed a rapid and durable clinical activity that improved with length of treatment.
ER -
KUTER, D. J., M. EFRAIM, Jiří MAYER, Marek TRNĚNÝ, V. MCDONALD, R. BIRD, T. REGENBOGEN, M. GARG, Z. KAPLAN, N. TZVETKOV, P. Y. CHOI, A. J. G. JANSEN, Milan KOSTAL, R. BAKER, Jaromir GUMULEC, E. J. LEE, I. CUNNINGHAM, I. GONCALVES, M. WARNER, R. BOCCIA, T. GERNSHEIMER, W. GHANIMA, O. BANDMAN, R. BURNS, A. NEALE, D. THOMAS, P. ARORA, B. ZHENG and Cooper N. RILZABRUTINIB. Rilzabrutinib, an Oral BTK Inhibitor, in Immune Thrombocytopenia. \textit{New England Journal of Medicine}. Waltham: Massachussetts Medical Society, 2022, vol.~386, No~15, p.~1421-1431. ISSN~0028-4793. Available from: https://dx.doi.org/10.1056/NEJMoa2110297.
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