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Safety and efficacy of oral panobinostat plus chemotherapy in patients aged 65 years or younger with high-risk acute myeloid leukemia.
Leuk Res 2019; 85:106197LR

Abstract

The role of histone deacetylase inhibitors in the treatment of acute myeloid leukemia (AML) is not well characterized. The current study evaluated the safety and efficacy of panobinostat in combination with idarubicin and cytarabine in newly diagnosed patients aged ≤65 years with primary or secondary high-risk AML based on cytogenetic classification. Treatment included fixed dose idarubicin (12 mg/m2/d, IV; day 1-3) and cytarabine (100 mg/m2/d, continuous IV infusion; day 1-7) and escalating oral doses of panobinostat at 15 mg, 20 mg, and 25 mg, thrice weekly starting at week 2 of a 28-day cycle. Forty-six patients were enrolled (primary AML [n = 36], secondary AML [n = 10]). The median age was 55 years. The most common all-grade AEs were diarrhea (54.3%), nausea (39.1%), vomiting, and decreased appetite (each, 21.7%), stomatitis (19.6%), and fatigue (17.4%). The overall response rate was 60.9%, 43.5% achieved a complete remission (CR), and 17.4% achieved CR with incomplete count recovery. The event-free survival at 1-year was 78.3%. Panobinostat in combination with idarubicin and cytarabine demonstrated tolerable safety and efficacy in younger patients with high-risk AML. The recommended phase 2 dose of panobinostat in this combination was 20 mg. ClinicalTrials.gov registry no: NCT01242774, and European Trial Registry EudraCT no: 2009-016809-42.

Authors+Show Affiliations

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. Electronic address: Daniel_Deangelo@dfci.harvard.edu.The Ohio State University Comprehensive Cancer Center, James Cancer Hospital, Columbus, Ohio, USA.NCT Trial Center, National Center for Tumor Diseases, Heidelberg, Germany.Hospital de la Santa Creu i Sant Pau, IIB Sant Pau and José Carreras Institute, Autonomous University of Barcelona, Spain.Stanford University School of Medicine, Stanford, California, USA.Hospital Universitario de Salamanca, Salamanca (IBSAL) y Centro de Investigación del Cáncer (IBMCC-CSIC), Salamanca, Spain.Universitätsklinikum Carl Gustav Carvus, Dresden, Germany.Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA.Kliniken der Med. Hochschule Hannover, Hannover, Germany.Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.Novartis Healthcare Pvt. Ltd., Hyderabad, India.Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.Medical University of South Carolina, Hollings Cancer Center, Charleston, South Carolina, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31541945

Citation

DeAngelo, Daniel J., et al. "Safety and Efficacy of Oral Panobinostat Plus Chemotherapy in Patients Aged 65 Years or Younger With High-risk Acute Myeloid Leukemia." Leukemia Research, vol. 85, 2019, p. 106197.
DeAngelo DJ, Walker AR, Schlenk RF, et al. Safety and efficacy of oral panobinostat plus chemotherapy in patients aged 65 years or younger with high-risk acute myeloid leukemia. Leuk Res. 2019;85:106197.
DeAngelo, D. J., Walker, A. R., Schlenk, R. F., Sierra, J., Medeiros, B. C., Ocio, E. M., ... Stuart, R. K. (2019). Safety and efficacy of oral panobinostat plus chemotherapy in patients aged 65 years or younger with high-risk acute myeloid leukemia. Leukemia Research, 85, p. 106197. doi:10.1016/j.leukres.2019.106197.
DeAngelo DJ, et al. Safety and Efficacy of Oral Panobinostat Plus Chemotherapy in Patients Aged 65 Years or Younger With High-risk Acute Myeloid Leukemia. Leuk Res. 2019;85:106197. PubMed PMID: 31541945.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Safety and efficacy of oral panobinostat plus chemotherapy in patients aged 65 years or younger with high-risk acute myeloid leukemia. AU - DeAngelo,Daniel J, AU - Walker,Alison R, AU - Schlenk,Richard F, AU - Sierra,Jorge, AU - Medeiros,Bruno C, AU - Ocio,Enrique M, AU - Röllig,Christoph, AU - Strickland,Stephen A, AU - Thol,Felicitas, AU - Valera,Sue-Zette, AU - Dasgupta,Kohinoor, AU - Berkowitz,Noah, AU - Stuart,Robert K, Y1 - 2019/08/01/ PY - 2018/05/03/received PY - 2019/07/12/revised PY - 2019/07/31/accepted PY - 2019/9/22/pubmed PY - 2019/9/22/medline PY - 2019/9/22/entrez KW - AML KW - Acute myeloid leukemia KW - Cytarabine KW - Idarubicin KW - Panobinostat SP - 106197 EP - 106197 JF - Leukemia research JO - Leuk. Res. VL - 85 N2 - The role of histone deacetylase inhibitors in the treatment of acute myeloid leukemia (AML) is not well characterized. The current study evaluated the safety and efficacy of panobinostat in combination with idarubicin and cytarabine in newly diagnosed patients aged ≤65 years with primary or secondary high-risk AML based on cytogenetic classification. Treatment included fixed dose idarubicin (12 mg/m2/d, IV; day 1-3) and cytarabine (100 mg/m2/d, continuous IV infusion; day 1-7) and escalating oral doses of panobinostat at 15 mg, 20 mg, and 25 mg, thrice weekly starting at week 2 of a 28-day cycle. Forty-six patients were enrolled (primary AML [n = 36], secondary AML [n = 10]). The median age was 55 years. The most common all-grade AEs were diarrhea (54.3%), nausea (39.1%), vomiting, and decreased appetite (each, 21.7%), stomatitis (19.6%), and fatigue (17.4%). The overall response rate was 60.9%, 43.5% achieved a complete remission (CR), and 17.4% achieved CR with incomplete count recovery. The event-free survival at 1-year was 78.3%. Panobinostat in combination with idarubicin and cytarabine demonstrated tolerable safety and efficacy in younger patients with high-risk AML. The recommended phase 2 dose of panobinostat in this combination was 20 mg. ClinicalTrials.gov registry no: NCT01242774, and European Trial Registry EudraCT no: 2009-016809-42. SN - 1873-5835 UR - https://www.unboundmedicine.com/medline/citation/31541945/Safety_and_efficacy_of_oral_panobinostat_plus_chemotherapy_in_patients_aged_65_years_or_younger_with_high-risk_acute_myeloid_leukemia L2 - https://linkinghub.elsevier.com/retrieve/pii/S0145-2126(19)30142-0 DB - PRIME DP - Unbound Medicine ER -