Activity of decitabine as maintenance therapy in core binding factor acute myeloid leukemia

Abstract

Background: Posttherapy measurable residual disease (MRD) positivity in core binding factor acute myeloid leukemia (CBF-AML) is associated with shorter relapse-free survival (RFS). Elimination of MRD measured via quantitative reverse transcription polymerase chain reaction (qRTPCR) for disease specific transcripts can potentially lead to better outcomes in CBF-AML.Methods: We prospectively monitored the MRD using qRTPCR and flow cytometry on bone marrow samples in patients with newly diagnosed CBF-AML who received decitabine (DAC) maintenance therapy after fludarabine/cytarabine/G-CSF (FLAG)based induction/consolidation regimen. Negative qRTPCR (CMR) was defined as fusion transcript <0.01%.Results: Thirty-one patients with CBF-AML including 14 with t(8;21) and 17 with inv(16) received parenteral DAC as maintenance therapy. Fifteen patients (48.3%) had completed FLAG-based induction/consolidation but with positive MRD (0.35%, range = 0.01%-0.91%) (Group 1). Sixteen patients (51.7%) could not complete recommended consolidations with FLAG-based regimen (due to older age or complications) and were switched to DAC maintenance (Group 2). In Group 2, eight patients (50%) had undetectable MRD (Group 2A) (all had qRTPCR ≤ 0.01%) and the other eight patients (50%) had residual fusion product by qRTPCR (0.1%, range = 0.02%-0.36%) (Group 2B) prior to starting DAC. Amongst the 23 patients who had a PCR ≥ 0.01% before maintenance therapy (Groups 1 and 2B), 12 patients (52%) attained a CMR as their best response (responders). The median pre-DAC qRTPCR amongst responders were 0.03% compared to 0.14% in nonresponders (p = .002). The median estimated molecular RFS amongst responders were 93.9 months. At a median

Hypomethylating agent monotherapy in core binding factor acute myeloid leukemia: a French multicentric retrospective study

“…One-year disease-free survival (DFS) was 80%, and did not statistically differ from reported DFS in non-CBF-AML patients. Senapati et alreported in a prospective study that decitabine maintenance in CBF-AML patients in CR1 after intensive chemotherapy with persistent molecular disease led to complete molecular response in 52% of cases ( n = 12/23) [ 54 ]. Nevertheless, even if the median molecular relapse free-survival in responders was 93.9 months, there was no difference in overall survival between responders and non-responders to HMA therapy.…”

Therapy-Related Core Binding Factor Acute Myeloid Leukemia

“…In t-CBF-AML in the presence of KIT mutation and with suboptimal qRT-PCR response or the persistence of qRT-PCR after 2 cycles of consolidation generally represents a subgroup with a high risk of relapse who would benefit from salvage therapy with an early donor search for allo-sct [ 62 , 75 ]. DAC maintenance can be considered in t-CBF-AML patients with low qRT-PCR positivity as described above but with early evaluation for allo-sct in the event that their low-level qRT-PCR positivity does not convert to MRD-negative status [ 34 , 76 ].…”

“…The importance of completing all scheduled cycles of definitive chemotherapy in the interest of long-term survival should be stressed to patients [ 43 ]. Those who are unable to complete definitive chemotherapy or who have persistent qRT-PCR positivity after 2 cycles of consolidation therapy and who have KIT mutations should be considered for allo-sct [ 62 , 75 , 76 , 85 , 86 ]. However, overall, outcomes data for allo-sct in t-CBF-AML remain insufficient.…”

Development of GBRT Model as a Novel and Robust Mathematical Model to Predict and Optimize the Solubility of Decitabine as an Anti-Cancer Drug

“…Decitabine (currently sold under the brand name DACOGEN ® ) is an intravenously administered chemotherapeutic drug, which acts as a nucleoside metabolic inhibitor [ 3 , 4 , 5 ]. Despite the emergence of some adverse events such as neutropenia, thrombocytopenia, and embryo–fetal toxicity in patients, the drug’s great efficiency in ameliorating MDS has encouraged researchers to use it extensively [ 6 , 7 , 8 ]. Having long been considered, the most important duty of research and development (R&D) centers of pharmaceutical companies has been to concentrate on the development of supercritical fluid technology (SCFT) [ 9 ].…”