Use of tamibarotene, a potent and selective RARα agonist, in combination with azacitidine in patients with relapsed and refractory AML with RARA gene overexpression Journal Article
| Authors: | 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. |
| Article Title: | 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: | 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. © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. |
| Keywords: | adult; clinical article; controlled study; aged; overall survival; genetics; leukemia, myeloid, acute; clinical feature; constipation; drug activity; fatigue; cancer combination chemotherapy; diarrhea; drug safety; cancer patient; cytarabine; antineoplastic agent; gene overexpression; low drug dose; multiple cycle treatment; phase 2 clinical trial; nausea; vomiting; antineoplastic combined chemotherapy protocols; cohort analysis; lomustine; arthralgia; febrile neutropenia; fever; myelodysplastic syndrome; biomarker; multicenter study; idarubicin; kaplan meier method; leukemia relapse; epistaxis; retinoid; hypertriglyceridemia; azacitidine; myelodysplastic syndromes; retinoic acid receptor alpha; decreased appetite; demographics; acute myeloid leukemia; tamibarotene; humans; human; male; female; article; venetoclax; cytarabine plus daunorubicin; rara; sy-1425 |
| Journal Title: | Leukemia and Lymphoma |
| Volume: | 64 |
| Issue: | 12 |
| ISSN: | 1042-8194 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 2023-01-01 |
| Start Page: | 1992 |
| End Page: | 2001 |
| Language: | English |
| DOI: | 10.1080/10428194.2023.2243356 |
| PUBMED: | 37571998 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
