A phase I study of the combination of palbociclib and dexamethasone for the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia.

Autor: Wilde L; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia, PA, United States. Electronic address: Lindsay.wilde@jefferson.edu., Porazzi P; Division of Hematology and Oncology and Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, United States., Trotta R; Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States., De Dominici M; Department of Biochemistry and Molecular Genetics, University of Colorado, Denver, CO, United States., Palmisiano N; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia, PA, United States., Keiffer G; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia, PA, United States., Rancani K; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia, PA, United States., Yingling K; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia, PA, United States., Calabretta B; Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States., Kasner M; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia, PA, United States.
Jazyk: angličtina
Zdroj: Leukemia research [Leuk Res] 2023 Jun; Vol. 129, pp. 107075. Date of Electronic Publication: 2023 Apr 06.
DOI: 10.1016/j.leukres.2023.107075
Abstrakt: Purpose: Despite advances in the treatment of B-cell acute lymphoblastic leukemia (B-ALL), outcomes for relapsed/refractory (R/R) disease remain poor. Preclinical studies suggest that the combination of the CDK4/6 inhibitor palbociclib and dexamethasone may be effective in targeting leukemic cell growth. We conducted a phase I study of escalating doses of palbociclib in combination with dexamethasone in adults with R/R B-ALL.
Methods: Cycle 1 consisted of single agent palbociclib given for 7 days and continued for 28 additional days in combination with dexamethasone 20 mg daily. Palbociclib dosing began at 100 mg daily. Patients with a response were eligible for maintenance consisting of 1 week of palbociclib plus dexamethasone (20 mg daily × 2 days, 16 mg daily × 2 days, 12 mg daily × 2 days, 6 mg daily × 1 day), followed by 3 weeks of palbociclib alone. Safety, efficacy, and the expression of phospho-RB and c-MYB/BCL-2 were measured.
Conclusions: Seven patients were treated on study before it was closed early due to slow accrual. No dose limiting toxicities were identified. One patient had a complete response with incomplete hematologic recovery, suggesting possible efficacy of the treatment. Reduction in CD34+ cells, p-RB, c-MYB, and BCL-2 expression also suggested on-target therapy effects.
Competing Interests: Declaration of Competing Interest MK reports research funding from Kartos/Telios, Gilead, Pfizer, and BMS and membership on advisory committees for Astellas and Kronos Bio. NP reports research funding from Genentech and AbbVie. The other authors of this manuscript report no relationships to disclose.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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