Combination romidepsin and azacitidine therapy is well tolerated and clinically active in adults with high-risk acute myeloid leukaemia ineligible for intensive chemotherapy.
Justin LokeMarlen MetznerRebecca BoucherAimee JacksonLouise HopkinsJiri PavluEleni TholouliMark DrummondAndy PeniketRebecca BishopSonia FoxParesh VyasCharles F CraddockPublished in: British journal of haematology (2021)
Azacitidine (AZA) is important in the management of patients with acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy. Romidepsin (ROM) is a histone deacetylase inhibitor which synergises with AZA in vitro. The ROMAZA trial established the maximum tolerated dose (MTD) of combined ROM/AZA therapy in patients with AML, as ROM 12 mg/m2 on Days 8 and 15, with AZA 75 mg/m2 administered for 7/28 day cycle. Nine of the 38 (23·7%) patients treated at the MTD were classified as responders by Cycle 6 (best response: complete remission [CR]/incomplete CR n = 7, partial response n = 2). Correlative next-generation sequencing studies demonstrated important insights into therapy resistance.
Keyphrases
- acute myeloid leukemia
- histone deacetylase
- bone marrow
- allogeneic hematopoietic stem cell transplantation
- clinical trial
- locally advanced
- squamous cell carcinoma
- randomized controlled trial
- mesenchymal stem cells
- immune response
- study protocol
- systemic lupus erythematosus
- gene expression
- respiratory failure
- cell therapy
- copy number
- drug induced