PCN121 Decitabine Reduces Transfusion Dependence in Older Patients With Acute Myeloid Leukaemia: Results From a Post-Hoc Analysis of a Randomised Phase III Trial

6632 Background: A phase III trial (NCT00260832) in patients (N=485) ≥65y with newly diagnosed acute myeloid leukemia (AML) was conducted (Kantarjian, JCO; in press). Every 4 wk, patients received decitabine (DAC) 20 mg/m2 (1-h intravenous infusion, 5 successive days) or treatment choice (TC) with either supportive care or cytarabine (20 mg/m2 subcutaneous injection daily, 10 successive days). This post hoc analysis examined whether baseline (BL) renal and hepatic function and white blood cell (WBC) counts were associated with response to DAC or TC. Methods: For patients with available data, BL WBC count and markers of renal function (blood urea nitrogen [BUN], creatinine) and liver function (ALT, AST, albumin) were tabulated for patients with/without a response to DAC or TC. Response was defined as morphologic complete remission (CR), CR with incomplete blood count recovery (CRi), or partial remission (PR). Results: Nonresponders had a higher mean BL creatinine vs responders (86.78 vs 80.23 mmol/L, respectively; P=.005); with no differences in BL BUN levels. There were no other between-group differences. Conclusions: This analysis suggests that there is no relationship between BL WBC or hepatic function and response to treatment with DAC or TC. Although there was no difference in BL BUN, higher mean creatinine levels in nonresponders may suggest a prognostic relationship but further studies are needed to clarify. [Table: see text]

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Post hoc analysis of association between treatment response and various indicators of efficacy and safety in a randomized phase III trial of decitabine in older patients with acute myeloid leukemia.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.6627 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 6627-6627

Author(s):

Mark D Minden ◽

Chris Arthur ◽

Jiri Mayer ◽

Mark M. Jones ◽

Peter G. Tarassoff ◽

...

Keyword(s):

Older Patients ◽

Myeloid Leukemia ◽

Antibiotic Use ◽

Phase Iii ◽

Newly Diagnosed ◽

Efficacy And Safety ◽

Phase Iii Trial ◽

Post Hoc Analysis ◽

Dose Modifications ◽

Post Hoc

6627 Background: In a recent, large phase III trial (NCT00260832; Kantarjian, JCO; in press), 485 patients ≥65y with newly diagnosed acute myeloid leukemia (AML) received, every 4 wks, treatment choice (TC) of either supportive care or cytarabine (20 mg/m2 subcutaneous injection, 10 consecutive days) or decitabine (DAC) 20 mg/m2 (1-h intravenous [IV] infusion, 5 consecutive days). This post hoc analysis investigated relationships between response to treatment and indicators of efficacy and safety. Methods: Response was defined as morphologic complete remission (CR), or CR with incomplete blood count recovery (CRi) or partial response (PR). Transfusions (red blood cell [RBC] or platelets [PLT]), IV antibiotic use, and dose modifications were tabulated for responders and nonresponders to DAC or TC during the treatment period. Results: Fewer responders than nonresponders had dose modifications (30.4% vs 64.5%, respectively; P<.0001). Antibiotic use and transfusions were similar in both groups. Overall survival for responders was 16.1–18.5 mo vs 4.2–4.9 mo for nonresponders. Conclusions: These data suggest that response to DAC or TC treatment predicts clinically relevant benefits, with fewer dose modifications in older patients with newly diagnosed AML. The number of transfusions and antibiotic use was impacted by the longer survival time of responders vs nonresponders. Data on the impact of early response are being analyzed. [Table: see text]

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Multicentre phase III trial on fludarabine, cytarabine (Ara-C), and idarubicin versus idarubicin, Ara-C and etoposide for induction treatment of younger, newly diagnosed acute myeloid leukaemia patients

British Journal of Haematology ◽

10.1111/j.1365-2141.2005.05745.x ◽

2005 ◽

Vol 131 (2) ◽

pp. 172-179 ◽

Cited By ~ 37

Author(s):

Domenico Russo ◽

Michele Malagola ◽

Antonio Vivo ◽

Mauro Fiacchini ◽

Giovanni Martinelli ◽

...

Keyword(s):

Acute Myeloid Leukaemia ◽

Myeloid Leukaemia ◽

Phase Iii ◽

Induction Treatment ◽

Newly Diagnosed ◽

Phase Iii Trial ◽

Multicentre Phase ◽

Acute Myeloid

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Post hoc analysis of relationship between baseline white blood cell count and survival outcome in a randomized phase III trial of decitabine in older patients with newly diagnosed acute myeloid leukemia.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.6559 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 6559-6559

Author(s):

Chris Arthur ◽

Jaroslav Cermak ◽

Jacques Delaunay ◽

Jiri Mayer ◽

Grzegorz Mazur ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Survival Outcome ◽

Phase Iii ◽

Newly Diagnosed ◽

Phase Iii Trial ◽

Post Hoc Analysis ◽

Wbc Count ◽

Post Hoc ◽

Acute Myeloid

6559 Background: In a large phase III trial (N=485), patients (pts) ≥65y with newly diagnosed acute myeloid leukemia (AML) received 1-h IV infusion of decitabine (DAC) 20 mg/m2 for 5 consecutive days every 4 wk or treatment choice (TC) with supportive care or cytarabine 20 mg/m2 subcutaneous injection for 10 consecutive days every 4 wk (NCT00260832; Kantarjian et al. JCO, in press). Enrolled pts had white blood cell (WBC) count <40 x109/L; baseline WBC counts were relatively low (median [range] DAC: 3.1 x109/L [0.3-127.0]; TC: 3.7 x109/L [0.5-80.9]). This post hoc analysis assessed baseline WBC count and survival outcome. Methods: Overall survival (OS) and progression-free survival (PFS) were summarized by baseline WBC subgroups (<1, 1-5, >5 x109/L). Results: Mature survival data (2010) were based on intent-to-treat (ITT) population (446 deaths: TC, n=227; DAC, n=219). OS was 5.0 mo for TC vs 7.7 mo for DAC (nominal P=.037). For each WBC subgroup, differences in OS for TC vs DAC were not significant (NS), but hazard ratios (HR) favored DAC for all subgroups (Table). There was a significant difference in PFS in favor of DAC for patients with baseline WBC 1–5 x109/L (P=.005; HR=0.67) and >5 x109/L (P=.027; HR=0.71). Conclusions: These data are consistent with overall results, with a trend toward improved outcome with DAC regardless of baseline WBC count in older pts with newly diagnosed AML. Further analyses are warranted. [Table: see text]

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