A phase 1b/2b multicenter study of oral panobinostat plus azacitidine in adults with MDS, CMML or AML with less than or equal to 30% blasts

Garcia-Manero, G, Sekeres, M A, Egyed, M, Breccia, M, Graux, C, Cavenagh, J D, Salman, H, Illes, A, Fenaux, P, DeAngelo, D J, Stauder, R, Yee, K, Zhu, N, Lee, J-H, Valcarcel, D, MacWhannell, A, Borbenyi, Z, Gazi, L, Acharyya, S, Ide, S, Marker, M and Ottmann, Oliver ORCID: https://orcid.org/0000-0001-9559-1330 2017. A phase 1b/2b multicenter study of oral panobinostat plus azacitidine in adults with MDS, CMML or AML with less than or equal to 30% blasts. Leukemia 31 (12) , pp. 2799-2806. 10.1038/leu.2017.159

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Abstract

Treatment with azacitidine (AZA), a demethylating agent, prolonged overall survival (OS) vs conventional care in patients with higher-risk myelodysplastic syndromes (MDS). As median survival with monotherapy is <2 years, novel agents are needed to improve outcomes. This phase 1b/2b trial (n=113) was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of panobinostat (PAN)+AZA (phase 1b) and evaluate the early efficacy and safety of PAN+AZA vs AZA monotherapy (phase 2b) in patients with higher-risk MDS, chronic myelomonocytic leukemia or oligoblastic acute myeloid leukemia with <30% blasts. The MTD was not reached; the RP2D was PAN 30 mg plus AZA 75 mg/m2. More patients receiving PAN+AZA achieved a composite complete response ([CR)+morphologic CR with incomplete blood count+bone marrow CR (27.5% (95% CI, 14.6–43.9%)) vs AZA (14.3% (5.4–28.5%)). However, no significant difference was observed in the 1-year OS rate (PAN+AZA, 60% (50–80%); AZA, 70% (50–80%)) or time to progression (PAN+AZA, 70% (40–90%); AZA, 70% (40–80%)). More grade 3/4 adverse events (97.4 vs 81.0%) and on-treatment deaths (13.2 vs 4.8%) occurred with PAN+AZA. Further dose or schedule optimization may improve the risk/benefit profile of this regimen.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Publisher:	Nature Publishing Group
ISSN:	0887-6924
Date of First Compliant Deposit:	27 July 2017
Date of Acceptance:	23 February 2017
Last Modified:	04 May 2023 03:13
URI:	https://orca.cardiff.ac.uk/id/eprint/103058

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