AbstractObjectiveWe aimed to retrospectively discern the heterogeneity of outcomes from clinicopathological characteristics and next‐generation sequencing (NGS) data in adult patients with NPM1‐mutated (NPM1mut) acute myeloid leukemia (AML) induced with standard‐dose (SD, 100–200 mg/m2) and intermediate‐dose (ID, 1000–2000 mg/m2) cytarabine arabinose (Ara‐C).MethodsIn the entire cohort and FLT3‐ITD subgroups, multivariate Logistic and Cox regression analyses were used to analyze the comprehensive complete remission (cCR) rate after one or two induction cycles, event‐free survival (EFS), and overall survival (OS).ResultsAmong a total of 203 NPM1mut patients evaluable for clinical outcome, 144 (70.9%) received a first SD‐Ara‐C induction and 59 (29.1%) received ID‐Ara‐C induction. Early death was recorded in seven (3.4%) after one or two cycles of induction. Focusing analysis on the NPM1mut/FLT3‐ITD(−) subgroup, independent factors showing inferior outcome were presence of TET2 mutation [cCR rate, OR = 12.82 (95%CI 1.93–85.28), p = 0.008; EFS, HR = 2.92 (95%CI 1.46–5.86), p = 0.003], increasing age [EFS, HR = 1.49 (95%CI 1.10–2.02), p = 0.012 by every 10‐years elevation], white blood cell count ≥60 × 109/L [EFS, HR = 3.30 (95%CI 1.63–6.70), p = 0.001], and ≥4 mutated genes at initial diagnosis [OS, HR = 5.54 (95%CI 1.77–17.33), p = 0.003]. In contrast, when focusing on the NPM1mut/FLT3‐ITD(+) subgroup, factors showing superior outcome were ID‐Ara‐C induction [cCR rate, OR = 0.20 (95%CI 0.05–0.81), p = 0.025; EFS, HR = 0.27 (95%CI 0.13–0.60), p = 0.001] and allo‐transplantation [OS, HR = 0.45 (95%CI 0.21–0.94), p = 0.033]. Factors showing inferior outcome included CD34(+) [cCR rate, OR = 6.22 (95%CI 1.86–20.77), p = 0.003; EFS, HR = 2.01 (95%CI 1.12–3.61), p = 0.020] and ≥5 mutated genes [OS, HR = 2.85 (95%CI 1.33–6.10), p = 0.007].ConclusionWe conclude that TET2(+), age, and white blood cell count convey an outcome risk modulation for AML with NPM1mut/FLT3‐ITD(−), as does CD34 and ID‐Ara‐C induction for NPM1mut/FLT3‐ITD(+). The findings permit re‐stratification of NPM1mut AML into distinct prognostic subsets to guide risk‐adapted individualized treatment.

01 Sep 2022·European Journal of Haematology

Efficacy of conventional‐dose cytarabine, idarubicin and thioguanine versus intermediate‐dose cytarabine and idarubicin in the induction treatment of acute myeloid leukemia: Long‐term results of the prospective randomized nationwide AML‐2003 study by the Finnish Leukemia Group

Article

Author: Kauppila, Marjut ; Kolonen, Aarne ; Koivunen, Elli ; Jantunen, Esa ; Pelliniemi, Tarja‐Terttu ; Penttilä, Karri ; Sinisalo, Marjatta ; Ollikainen, Hanna ; Ruutu, Tapani ; Sankelo, Marja ; Rimpiläinen, Johanna ; Pyörälä, Marja ; Volin, Liisa ; Itälä‐Remes, Maija ; Elonen, Erkki ; Kuittinen, Taru ; Porkka, Kimmo ; Säily, Marjaana ; Nousiainen, Tapio ; Rintala, Hannele ; Huhtala, Heini ; Silvennoinen, Raija ; Rauhala, Auvo ; Räty, Riikka ; Kairisto, Veli ; Koistinen, Pirjo

AbstractObjectivesAML‐2003 study sought to compare the long‐term efficacy and safety of IAT and IdAraC‐Ida in induction chemotherapy of acute myeloid leukemia (AML) and introduce the results of an integrated genetic and clinical risk classification guided treatment strategy.MethodsPatients were randomized to receive either IAT or IdAraC‐Ida as the first induction treatment. Intensified postremission strategies were employed based on measurable residual disease (MRD) and risk classification. Structured questionnaire forms were used to gather data prospectively.ResultsA total of 356 AML patients with a median age of 53 years participated in the study. Long‐term overall survival (OS) and relapse‐free survival (RFS) were both 49% at 10 years. The median follow‐up was 114 months. No significant difference in remission rate, OS or RFS was observed between the two induction treatments. Risk classification according to the protocol, MRD after the first and the last consolidation treatment affected the OS and RFS significantly (p < .001).ConclusionsIntensified cytarabine dose in the first induction treatment was not better than IAT in patients with AML. Intensification of postremission treatment in patients with clinical risk factors or MRD seems reasonable, but randomized controlled studies are warranted in the future.

01 Jun 2022·Journal of Cancer Research and Clinical OncologyQ3 · MEDICINE

Impact of induction chemotherapy with intermediate-dosed cytarabine and subsequent allogeneic stem cell transplantation on the outcome of high-risk acute myeloid leukemia

Q3 · MEDICINE

Article

Author: Scholl, Sebastian ; Schrenk, Karin ; Sayer, Herbert G ; Fleischmann, Maximilian ; Hochhaus, Andreas ; Schnetzke, Ulf ; Hammersen, Jakob ; Frietsch, Jochen J ; Hilgendorf, Inken ; Glaser, Anita

AbstractBackgroundAcute myeloid leukemia (AML) with antecedent hematological disease (s-AML) and treatment-related AML (t-AML) predicts poor prognosis. Intensive treatment protocols of those high-risk patients should consider allogeneic stem cell transplantation (allo-HSCT) in first complete remission (CR). Despite allo-HSCT, relapse rate remains high. Induction chemotherapy with liposomal cytarabine and daunorubicin (CPX-351) has been approved for patients with AML with myeloid-related changes (AML-MRC) or t-AML based on improved survival and remission rates compared to standard 7 + 3 induction.Patients and methods110 patients with newly diagnosed s-AML or t-AML at a university hospital were analyzed retrospectively. Median age was 62 years (24–77 years). A total of 65 patients with s-AML after MDS (59%) and 23 patients (20.9%) with t-AML were included. Induction chemotherapy consisted of intermediate-dosed cytarabine (ID-AraC) in combination with idarubicin (patients up to 60 years) or mitoxantrone (patients over 60 years). In patients subsequently undergoing allo-HSCT, reduced conditioning regimens (RIC) were applied prior to transplantation in 47 of 62 patients (76%).ResultsInduction chemotherapy with ID-AraC resulted in an overall response rate of 83% including complete remission (CR/CRi) in 69 patients (63%) with a low rate of early death (2.7%). Most relevant non-hematologic toxicity consisted of infectious complications including sepsis with need of intensive care treatment in five patients (4.5%) and proven or probable invasive fungal disease in eight patients (7.2%). Relapse-free survival (RFS), event-free survival (EFS) and overall survival (OS) of the whole cohort were 19 months (0–167), 10 months (0–234) and 15 months (0–234), respectively (p < 0.0001). A significant improvement of OS was observed in patients who underwent allo-HSCT compared to those without subsequent allo-HSCT: 9 vs. 46 months, p < 0.0001. Rate of transplantation-related mortality (TRM) in the early phase post allo-HSCT was low (0.9% at day 30 and 1.8% at day 90, respectively). RIC conditioning results in OS rate of 60% after 60 months post allo-HSCT (median OS not reached).ConclusionS-AML and t-AML patients receiving induction chemotherapy with intermediate-dosed cytarabine showed satisfactory response rate and consolidation therapy with allo-HSCT after full or reduced-intensity conditioning further improved survival in these patients with similar outcome as reported for CPX-351.

100 Deals associated with Floctafenine

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D01267	Floctafenine	N02BG04	DB08976

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