Use of tamibarotene, a potent and selective RARα agonist, in combination with azacitidine in patients with relapsed and refractory AML with RARA gene overexpression

Eytan M. Stein; Stephane de Botton; Thomas Cluzeau; Arnaud Pigneux; Jane L. Liesveld; Rachel J. Cook; Philippe Rousselot; David A. Rizzieri; Thorsten Braun; Gail J. Roboz; Delphine Lebon; Mael Heiblig; Kristen Baker; Angela Volkert; Sofia Paul; Nisha Rajagopal; David A. Roth; Michael Kelly; Pierre Peterlin

doi:10.1080/10428194.2023.2243356

Use of tamibarotene, a potent and selective RARα agonist, in combination with azacitidine in patients with relapsed and refractory AML with RARA gene overexpression

Eytan M. Stein, Stephane de Botton, Thomas Cluzeau, Arnaud Pigneux, Jane L. Liesveld, Rachel J. Cook, Philippe Rousselot, David A. Rizzieri, Thorsten Braun, Gail J. Roboz, Delphine Lebon, Mael Heiblig, Kristen Baker, Angela Volkert, Sofia Paul, Nisha Rajagopal, David A. Roth, Michael Kelly, Pierre Peterlin

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Tamibarotene-based therapy is a novel targeted approach for the treatment of relapsed/refractory (R/R) acute myeloid leukemia (AML) with retinoic acid receptor alpha (RARA) gene overexpression. Approximately, 50% of higher-risk myelodysplastic syndrome (MDS) patients and approximately 30% of AML patients are positive for RARA overexpression using a blood-based biomarker test that measures RARA expression in peripheral blasts. A phase 2 study investigating the activity of tamibarotene in patients with RARA overexpression was conducted in patients with AML and MDS (NCT02807558). In 28 patients with R/R AML and RARA overexpression treated with tamibarotene in combination with azacitidine, the median overall survival was 5.9 months. In 21 response-evaluable patients, the complete remission/complete remission with incomplete hematologic recovery (CR/CRi) rate was 19%, and median time to initial CR/CRi was 1.2 months. The favorable safety profile and preliminary clinical activity support the development of combination therapies with tamibarotene in myeloid malignancies with RARA overexpression.

Original language	English (US)
Pages (from-to)	1992-2001
Number of pages	10
Journal	Leukemia and Lymphoma
Volume	64
Issue number	12
DOIs	https://doi.org/10.1080/10428194.2023.2243356
State	Published - 2023

Keywords

Biomarker
RARA
SY-1425
retinoid
tamibarotene

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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10.1080/10428194.2023.2243356

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Stein, E. M., de Botton, S., Cluzeau, T., Pigneux, A., Liesveld, J. L., Cook, R. J., Rousselot, P., Rizzieri, D. A., Braun, T., Roboz, G. J., Lebon, D., Heiblig, M., Baker, K., Volkert, A., Paul, S., Rajagopal, N., Roth, D. A., Kelly, M., & Peterlin, P. (2023). Use of tamibarotene, a potent and selective RARα agonist, in combination with azacitidine in patients with relapsed and refractory AML with RARA gene overexpression. Leukemia and Lymphoma, 64(12), 1992-2001. https://doi.org/10.1080/10428194.2023.2243356

Stein, EM, de Botton, S, Cluzeau, T, Pigneux, A, Liesveld, JL, Cook, RJ, Rousselot, P, Rizzieri, DA, Braun, T, Roboz, GJ, Lebon, D, Heiblig, M, Baker, K, Volkert, A, Paul, S, Rajagopal, N, Roth, DA, Kelly, M & Peterlin, P 2023, 'Use of tamibarotene, a potent and selective RARα agonist, in combination with azacitidine in patients with relapsed and refractory AML with RARA gene overexpression', Leukemia and Lymphoma, vol. 64, no. 12, pp. 1992-2001. https://doi.org/10.1080/10428194.2023.2243356

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abstract = "Tamibarotene-based therapy is a novel targeted approach for the treatment of relapsed/refractory (R/R) acute myeloid leukemia (AML) with retinoic acid receptor alpha (RARA) gene overexpression. Approximately, 50% of higher-risk myelodysplastic syndrome (MDS) patients and approximately 30% of AML patients are positive for RARA overexpression using a blood-based biomarker test that measures RARA expression in peripheral blasts. A phase 2 study investigating the activity of tamibarotene in patients with RARA overexpression was conducted in patients with AML and MDS (NCT02807558). In 28 patients with R/R AML and RARA overexpression treated with tamibarotene in combination with azacitidine, the median overall survival was 5.9 months. In 21 response-evaluable patients, the complete remission/complete remission with incomplete hematologic recovery (CR/CRi) rate was 19%, and median time to initial CR/CRi was 1.2 months. The favorable safety profile and preliminary clinical activity support the development of combination therapies with tamibarotene in myeloid malignancies with RARA overexpression.",

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AU - Cluzeau, Thomas

AU - Pigneux, Arnaud

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AU - Rizzieri, David A.

AU - Braun, Thorsten

AU - Roboz, Gail J.

AU - Lebon, Delphine

AU - Heiblig, Mael

AU - Baker, Kristen

AU - Volkert, Angela

AU - Paul, Sofia

AU - Rajagopal, Nisha

AU - Roth, David A.

AU - Kelly, Michael

AU - Peterlin, Pierre

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N2 - Tamibarotene-based therapy is a novel targeted approach for the treatment of relapsed/refractory (R/R) acute myeloid leukemia (AML) with retinoic acid receptor alpha (RARA) gene overexpression. Approximately, 50% of higher-risk myelodysplastic syndrome (MDS) patients and approximately 30% of AML patients are positive for RARA overexpression using a blood-based biomarker test that measures RARA expression in peripheral blasts. A phase 2 study investigating the activity of tamibarotene in patients with RARA overexpression was conducted in patients with AML and MDS (NCT02807558). In 28 patients with R/R AML and RARA overexpression treated with tamibarotene in combination with azacitidine, the median overall survival was 5.9 months. In 21 response-evaluable patients, the complete remission/complete remission with incomplete hematologic recovery (CR/CRi) rate was 19%, and median time to initial CR/CRi was 1.2 months. The favorable safety profile and preliminary clinical activity support the development of combination therapies with tamibarotene in myeloid malignancies with RARA overexpression.

AB - Tamibarotene-based therapy is a novel targeted approach for the treatment of relapsed/refractory (R/R) acute myeloid leukemia (AML) with retinoic acid receptor alpha (RARA) gene overexpression. Approximately, 50% of higher-risk myelodysplastic syndrome (MDS) patients and approximately 30% of AML patients are positive for RARA overexpression using a blood-based biomarker test that measures RARA expression in peripheral blasts. A phase 2 study investigating the activity of tamibarotene in patients with RARA overexpression was conducted in patients with AML and MDS (NCT02807558). In 28 patients with R/R AML and RARA overexpression treated with tamibarotene in combination with azacitidine, the median overall survival was 5.9 months. In 21 response-evaluable patients, the complete remission/complete remission with incomplete hematologic recovery (CR/CRi) rate was 19%, and median time to initial CR/CRi was 1.2 months. The favorable safety profile and preliminary clinical activity support the development of combination therapies with tamibarotene in myeloid malignancies with RARA overexpression.

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Use of tamibarotene, a potent and selective RARα agonist, in combination with azacitidine in patients with relapsed and refractory AML with RARA gene overexpression

Abstract

Keywords

ASJC Scopus subject areas

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