PortalPublikationenAvapritinib versus Placebo in Indolent Systemic Mastocytosis

Avapritinib versus Placebo in Indolent Systemic Mastocytosis

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Avapritinib versus Placebo in Indolent Systemic Mastocytosis. / Gotlib, Jason; Castells, Mariana; Elberink, Hanneke Oude; Siebenhaar, Frank; Hartmann, Karin; Broesby-Olsen, Sigurd; George, Tracy I.; Panse, Jens; Alvarez-Twose, Iván; Radia, Deepti H.; Tashi, Tsewang; Bulai Livideanu, Cristina; Sabato, Vito; Heaney, Mark; Van Daele, Paul; Cerquozzi, Sonia; Dybedal, Ingunn; Reiter, Andreas; Pongdee, Thanai; Barete, Stéphane; Ustun, Celalettin; Schwartz, Lawrence; Ward, Brant R.; Schafhausen, Philippe; Vadas, Peter; Bose, Prithviraj; DeAngelo, Daniel J.; Rein, Lindsay; Vachhani, Pankit; Triggiani, Massimo; Bonadonna, Patrizia; Rafferty, Mark; Butt, Nauman M.; Oh, Stephen T.; Wortmann, Friederike; Ungerstedt, Johanna; Guilarte, Mar; Taparia, Minakshi; Kuykendall, Andrew T.; Arana Yi, Cecilia; Ogbogu, Princess; Gaudy-Marqueste, Caroline; Mattsson, Mattias; Shomali, William; Giannetti, Matthew P.; Bidollari, Ilda; Lin, Hui-Min; Sulllivan, Erin; Mar, Brenton; Maurer, Marcus.

in: NEJM Evidence, Jahrgang 2023, Nr. 2, 6, 23.05.2023.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Gotlib, J, Castells, M, Elberink, HO, Siebenhaar, F, Hartmann, K, Broesby-Olsen, S, George, TI, Panse, J, Alvarez-Twose, I, Radia, DH, Tashi, T, Bulai Livideanu, C, Sabato, V, Heaney, M, Van Daele, P, Cerquozzi, S, Dybedal, I, Reiter, A, Pongdee, T, Barete, S, Ustun, C, Schwartz, L, Ward, BR, Schafhausen, P, Vadas, P, Bose, P, DeAngelo, DJ, Rein, L, Vachhani, P, Triggiani, M, Bonadonna, P, Rafferty, M, Butt, NM, Oh, ST, Wortmann, F, Ungerstedt, J, Guilarte, M, Taparia, M, Kuykendall, AT, Arana Yi, C, Ogbogu, P, Gaudy-Marqueste, C, Mattsson, M, Shomali, W, Giannetti, MP, Bidollari, I, Lin, H-M, Sulllivan, E, Mar, B & Maurer, M 2023, 'Avapritinib versus Placebo in Indolent Systemic Mastocytosis', NEJM Evidence, Jg. 2023, Nr. 2, 6. https://doi.org/10.1056/EVIDoa2200339

APA

Gotlib, J., Castells, M., Elberink, H. O., Siebenhaar, F., Hartmann, K., Broesby-Olsen, S., George, T. I., Panse, J., Alvarez-Twose, I., Radia, D. H., Tashi, T., Bulai Livideanu, C., Sabato, V., Heaney, M., Van Daele, P., Cerquozzi, S., Dybedal, I., Reiter, A., Pongdee, T., ... Maurer, M. (2023). Avapritinib versus Placebo in Indolent Systemic Mastocytosis. NEJM Evidence, 2023(2), [6]. https://doi.org/10.1056/EVIDoa2200339

Vancouver

Gotlib J, Castells M, Elberink HO, Siebenhaar F, Hartmann K, Broesby-Olsen S et al. Avapritinib versus Placebo in Indolent Systemic Mastocytosis. NEJM Evidence. 2023 Mai 23;2023(2). 6. https://doi.org/10.1056/EVIDoa2200339

Bibtex

@article{ad3ecba5982f4108a82e9fb50e3e74b5,
title = "Avapritinib versus Placebo in Indolent Systemic Mastocytosis",
abstract = "BACKGROUNDIndolent systemic mastocytosis (ISM) is a clonal mast-cell disease driven by the KIT D816V mutation. We assessed the efficacy and safety of avapritinib versus placebo, both with best supportive care, in patients with ISM.METHODSWe randomized patients with moderate to severe ISM (total symptom score [TSS] of ≥28; scores range from 0 to 110, with higher numbers indicating more severe symptoms) two to one to avapritinib 25 mg once daily (n=141) or placebo (n=71). The primary end point was mean change in TSS based on the 14-day average of patient-reported severity of 11 symptoms. Secondary end points included reductions in serum tryptase and blood KIT D816V variant allele fraction (≥50%), reductions in TSS (≥50% and ≥30%), reduction in bone marrow mast cells (≥50%), and quality of life measures.RESULTSFrom baseline to week 24, avapritinib-treated patients had a decrease of 15.6 points (95% CI, −18.6 to −12.6) in TSS compared to a decrease of 9.2 points (−13.1 to −5.2) in the placebo group; P<0.003. From baseline to Week 24, 76/141 patients (54%; 45% to 62%) in the avapritinib group compared to 0/71 patients in the placebo group achieved a ≥50% reduction in serum tryptase level; P<0.001. Edema and increases in alkaline phosphatase were more common with avapritinib than placebo; there were few treatment discontinuations because of adverse events.CONCLUSIONSIn this trial, avapritinib was superior to placebo in reducing uncontrolled symptoms and mast-cell burden in patients with ISM. The long-term safety and efficacy of this approach for patients with ISM remain the focus of the ongoing trial. (Funded by Blueprint Medicines Corporation; ClinicalTrials.gov number, NCT03731260.)",
author = "Jason Gotlib and Mariana Castells and Elberink, {Hanneke Oude} and Frank Siebenhaar and Karin Hartmann and Sigurd Broesby-Olsen and George, {Tracy I.} and Jens Panse and Iv{\'a}n Alvarez-Twose and Radia, {Deepti H.} and Tsewang Tashi and {Bulai Livideanu}, Cristina and Vito Sabato and Mark Heaney and {Van Daele}, Paul and Sonia Cerquozzi and Ingunn Dybedal and Andreas Reiter and Thanai Pongdee and St{\'e}phane Barete and Celalettin Ustun and Lawrence Schwartz and Ward, {Brant R.} and Philippe Schafhausen and Peter Vadas and Prithviraj Bose and DeAngelo, {Daniel J.} and Lindsay Rein and Pankit Vachhani and Massimo Triggiani and Patrizia Bonadonna and Mark Rafferty and Butt, {Nauman M.} and Oh, {Stephen T.} and Friederike Wortmann and Johanna Ungerstedt and Mar Guilarte and Minakshi Taparia and Kuykendall, {Andrew T.} and {Arana Yi}, Cecilia and Princess Ogbogu and Caroline Gaudy-Marqueste and Mattias Mattsson and William Shomali and Giannetti, {Matthew P.} and Ilda Bidollari and Hui-Min Lin and Erin Sulllivan and Brenton Mar and Marcus Maurer",
year = "2023",
month = may,
day = "23",
doi = "10.1056/EVIDoa2200339",
language = "English",
volume = "2023",
number = "2",

}

RIS

TY - JOUR

T1 - Avapritinib versus Placebo in Indolent Systemic Mastocytosis

AU - Gotlib, Jason

AU - Castells, Mariana

AU - Elberink, Hanneke Oude

AU - Siebenhaar, Frank

AU - Hartmann, Karin

AU - Broesby-Olsen, Sigurd

AU - George, Tracy I.

AU - Panse, Jens

AU - Alvarez-Twose, Iván

AU - Radia, Deepti H.

AU - Tashi, Tsewang

AU - Bulai Livideanu, Cristina

AU - Sabato, Vito

AU - Heaney, Mark

AU - Van Daele, Paul

AU - Cerquozzi, Sonia

AU - Dybedal, Ingunn

AU - Reiter, Andreas

AU - Pongdee, Thanai

AU - Barete, Stéphane

AU - Ustun, Celalettin

AU - Schwartz, Lawrence

AU - Ward, Brant R.

AU - Schafhausen, Philippe

AU - Vadas, Peter

AU - Bose, Prithviraj

AU - DeAngelo, Daniel J.

AU - Rein, Lindsay

AU - Vachhani, Pankit

AU - Triggiani, Massimo

AU - Bonadonna, Patrizia

AU - Rafferty, Mark

AU - Butt, Nauman M.

AU - Oh, Stephen T.

AU - Wortmann, Friederike

AU - Ungerstedt, Johanna

AU - Guilarte, Mar

AU - Taparia, Minakshi

AU - Kuykendall, Andrew T.

AU - Arana Yi, Cecilia

AU - Ogbogu, Princess

AU - Gaudy-Marqueste, Caroline

AU - Mattsson, Mattias

AU - Shomali, William

AU - Giannetti, Matthew P.

AU - Bidollari, Ilda

AU - Lin, Hui-Min

AU - Sulllivan, Erin

AU - Mar, Brenton

AU - Maurer, Marcus

PY - 2023/5/23

Y1 - 2023/5/23

N2 - BACKGROUNDIndolent systemic mastocytosis (ISM) is a clonal mast-cell disease driven by the KIT D816V mutation. We assessed the efficacy and safety of avapritinib versus placebo, both with best supportive care, in patients with ISM.METHODSWe randomized patients with moderate to severe ISM (total symptom score [TSS] of ≥28; scores range from 0 to 110, with higher numbers indicating more severe symptoms) two to one to avapritinib 25 mg once daily (n=141) or placebo (n=71). The primary end point was mean change in TSS based on the 14-day average of patient-reported severity of 11 symptoms. Secondary end points included reductions in serum tryptase and blood KIT D816V variant allele fraction (≥50%), reductions in TSS (≥50% and ≥30%), reduction in bone marrow mast cells (≥50%), and quality of life measures.RESULTSFrom baseline to week 24, avapritinib-treated patients had a decrease of 15.6 points (95% CI, −18.6 to −12.6) in TSS compared to a decrease of 9.2 points (−13.1 to −5.2) in the placebo group; P<0.003. From baseline to Week 24, 76/141 patients (54%; 45% to 62%) in the avapritinib group compared to 0/71 patients in the placebo group achieved a ≥50% reduction in serum tryptase level; P<0.001. Edema and increases in alkaline phosphatase were more common with avapritinib than placebo; there were few treatment discontinuations because of adverse events.CONCLUSIONSIn this trial, avapritinib was superior to placebo in reducing uncontrolled symptoms and mast-cell burden in patients with ISM. The long-term safety and efficacy of this approach for patients with ISM remain the focus of the ongoing trial. (Funded by Blueprint Medicines Corporation; ClinicalTrials.gov number, NCT03731260.)

AB - BACKGROUNDIndolent systemic mastocytosis (ISM) is a clonal mast-cell disease driven by the KIT D816V mutation. We assessed the efficacy and safety of avapritinib versus placebo, both with best supportive care, in patients with ISM.METHODSWe randomized patients with moderate to severe ISM (total symptom score [TSS] of ≥28; scores range from 0 to 110, with higher numbers indicating more severe symptoms) two to one to avapritinib 25 mg once daily (n=141) or placebo (n=71). The primary end point was mean change in TSS based on the 14-day average of patient-reported severity of 11 symptoms. Secondary end points included reductions in serum tryptase and blood KIT D816V variant allele fraction (≥50%), reductions in TSS (≥50% and ≥30%), reduction in bone marrow mast cells (≥50%), and quality of life measures.RESULTSFrom baseline to week 24, avapritinib-treated patients had a decrease of 15.6 points (95% CI, −18.6 to −12.6) in TSS compared to a decrease of 9.2 points (−13.1 to −5.2) in the placebo group; P<0.003. From baseline to Week 24, 76/141 patients (54%; 45% to 62%) in the avapritinib group compared to 0/71 patients in the placebo group achieved a ≥50% reduction in serum tryptase level; P<0.001. Edema and increases in alkaline phosphatase were more common with avapritinib than placebo; there were few treatment discontinuations because of adverse events.CONCLUSIONSIn this trial, avapritinib was superior to placebo in reducing uncontrolled symptoms and mast-cell burden in patients with ISM. The long-term safety and efficacy of this approach for patients with ISM remain the focus of the ongoing trial. (Funded by Blueprint Medicines Corporation; ClinicalTrials.gov number, NCT03731260.)

U2 - 10.1056/EVIDoa2200339

DO - 10.1056/EVIDoa2200339

M3 - SCORING: Journal article

VL - 2023

IS - 2

M1 - 6

ER -