scholarly journals An evaluation of overall survival in patients with newly diagnosed acute myeloid leukemia and the relationship with glasdegib treatment and exposure

2020 ◽  
Vol 86 (4) ◽  
pp. 451-459
Author(s):  
Swan Lin ◽  
Naveed Shaik ◽  
Geoffrey Chan ◽  
Jorge E. Cortes ◽  
Ana Ruiz-Garcia
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Survival Benefit ◽  
Myeloid Leukemia ◽  
Time Course ◽  
The United States ◽  
Population Pharmacokinetic ◽  
Newly Diagnosed ◽  
Risk Of Death ◽  
Acute Myeloid

Abstract Purpose Glasdegib, an oral inhibitor of the Hedgehog signaling pathway, is approved in the United States in combination with low-dose cytarabine (LDAC) to treat patients with newly diagnosed acute myeloid leukemia (AML) ineligible to receive intensive chemotherapy. This population pharmacokinetic/pharmacodynamic analysis characterized the time course of survival with glasdegib + LDAC relative to LDAC alone, and explored whether the differences in glasdegib exposure at the clinical dose of 100 mg once daily (QD) significantly affected overall survival (OS). Methods Data from the BRIGHT AML 1003 trial in patients with AML were included in treatment–response (glasdegib + LDAC, n = 78; LDAC alone, n = 38) and exposure–response (glasdegib + LDAC, n = 75) analyses. Results The analyses demonstrate that patients treated with glasdegib + LDAC (vs LDAC alone) at any time point during the study period were 58% less likely to die, translating to prolonging of median OS by ~ 5 months (hazard ratio 0.42 [95% confidence interval 0.28–0.66]). Variability in glasdegib exposures did not impact the risk of death. Additionally, potential covariates such as patient demographics, prior treatment with a hypomethylating agent, baseline safety laboratory values, and disease characteristics, did not impact the probability of OS. Conclusion Together these results confirm that glasdegib + LDAC treatment (vs. LDAC alone) is associated with a significant survival benefit in patients with newly diagnosed AML, and that variability in glasdegib doses (e.g., for dose reductions) and exposures do not compromise the survival benefit of glasdegib 100 mg QD. Clinical Trial number NCT01546038.

Body mass index (BMI) influence on survival in adult patients with newly diagnosed acute myeloid leukemia (AML)/high-risk MDS: Retrospective study of 130 patients from a single institution.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e18011-e18011
Author(s):  
Mohamed Abdelfatah ◽  
Ali Al-Ameri ◽  
Zeyad Kanaan ◽  
Ahmed Malkawi ◽  
Nairmeen Awad Haller
Keyword(s):  
Body Mass Index ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Median Survival ◽  
Survival Benefit ◽  
Myeloid Leukemia ◽  
Normal Weight ◽  
Adult Patients ◽  
Newly Diagnosed ◽  
Acute Myeloid

e18011 Background: The incidence of obesity is increasing worldwide and is associated with numerous adverse health outcomes. In AML high body mass index (BMI) is associated with increased risk of treatment-related complications; the overall survival in patients with acute myeloid leukemia is inferior, with most studies conducted in the pediatric population. Aim: To evaluate the effect of increasing (BMI) in the overall survival (OS) of adult patients with AML/High risk MDS. Methods: After obtaining IRB approval, all adult patients with AML diagnosed and treated at our institution (2002–2010) were studied. Data collection included patient demographics, laboratory tests, bone marrow biopsies, BMI, and survival information. We classified the AML patients into two groups according to BMI (kg/m2) classification by WHO; normal Weight 18-25 kg/m2, overweight and obese >25 kg/m2. Chi-Square and T-test were used for between group comparisons and Kaplan-Meier test was applied for survival estimates. Results: Adult patients with newly diagnosed AML (n = 130) had a median age of 55 years (range: 19-90), and 43 (56%) patients were older than 75 years. Seventy-two patients (55%) were male and 58 (45%) were female. 45 patients (35%) in total had complex cytogenetics, 20 patients (15%) had AML arise from MDS.Forty-four patients (34%) were considered normal weight; Eighty-six patients (66%) were classified as overweight or obese. Overall median survival was 28 weeks; patients with BMI 18-25 kg/m2 had a 36-week median survival, while patients with BMI <25 kg/m2 had a 25-week median survival (p<0.499). Conclusions: Overall survival was low in the study population; survival in obese and overweight patients (BMI>25) was slightly lower than normal weight group (18-25 kg/m2), although this did not translate into a survival benefit. Future large scale studies may be needed to further define the role of BMI in survival benefit for these patients.

Phase 3 VERONA study of venetoclax with azacitidine to assess change in complete remission and overall survival in treatment-naïve higher-risk myelodysplastic syndromes.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS7054-TPS7054
Author(s):  
Amer Methqal Zeidan ◽  
Jacqueline Suen Garcia ◽  
Pierre Fenaux ◽  
Uwe Platzbecker ◽  
Yasushi Miyazaki ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Hypomethylating Agents ◽  
Newly Diagnosed ◽  
Phase 3 ◽  
Transfusion Independence ◽  
Treatment Naïve ◽  
The U.S ◽  
Acute Myeloid

TPS7054 Background: Patients with higher-risk myelodysplastic syndromes (HR-MDS) experience peripheral cytopenias, disease progression to acute myeloid leukemia, and high mortality with expected median overall survival of less than 2 years. Allogeneic hematopoietic cell transplantation (allo-HCT) is the only potentially curative treatment. Patients ineligible for transplantation are treated with hypomethylating agents such as azacitidine (Aza), which is not curative and provides limited improvement in clinical benefit. Venetoclax (Ven) is a selective, potent, oral B-cell lymphoma-2 (BCL-2) inhibitor that is approved in the U.S. in combination with hypomethylating agents for treating older or co-morbid patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy. Ven is approved in the U.S. as first-line treatment for chronic lymphocytic leukemia or small lymphocytic lymphoma. For patients with treatment-naïve HR-MDS, Ven + Aza demonstrated manageable safety and a combined complete remission (CR)/marrow CR (mCR) rate of 79% in a single arm phase 1b study (NCT02942290). To confirm these benefits, the VERONA study, a randomized, double-blind, phase 3 study (NCT04401748) of patients with treatment-naïve HR-MDS, will assess the safety and efficacy of Ven combined with Aza including CR rate and overall survival. Methods: Patients (≥18 years) with newly diagnosed HR-MDS per WHO 2016 classification with = 20% bone marrow blasts per marrow biopsy/aspirate at screening will be enrolled at ̃200 sites globally (̃500 patients). Patients must have intermediate risk or higher IPSS-R (score > 3), ECOG ≤2, and be hematopoietic stem cell transplant (HSCT) eligible without any pre-arranged donor, or HSCT ineligible without a plan for HSCT at Study Day 1. De novo patients without prior hypomethylating agents, chemotherapy for MDS, or allogenic stem cell transplantation are eligible. Patients will be randomized 1:1 to receive placebo or Ven 400 mg oral tablet once daily on Days 1-14, both in combination with Aza 75 mg/m2 (intravenous or subcutaneous) on Days 7-0-0 or Days 5-2-2 per 28-days. Patients will receive study treatment until disease progression, unacceptable toxicity, HCT, withdrawal of consent, or discontinuation. The primary endpoints are CR rate (as adjudicated by investigator) per IWG 2006 criteria and overall survival. Secondary outcomes are red blood cell transfusion independence, platelet transfusion independence, change in fatigue as measured by Patient-Reported Outcomes Measurement Information System (PROMIS)-fatigue SF 7a scale score, time to deterioration in physical functioning domain of EORTC QLC-C30 scale, overall response (CR + partial response), and modified overall response (CR + mCR + partial response). Exploratory objectives are predictive biomarkers and pharmacokinetics. Clinical trial information: NCT04401748.

scholarly journals CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia

2018 ◽  
Vol 36 (26) ◽  
pp. 2684-2692 ◽  
Author(s):  
Jeffrey E. Lancet ◽  
Geoffrey L. Uy ◽  
Jorge E. Cortes ◽  
Laura F. Newell ◽  
Tara L. Lin ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Bone Marrow Cells ◽  
Remission Rate ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Secondary Acute Myeloid Leukemia ◽  
Acute Myeloid

Purpose CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic 5:1 drug ratio into leukemia cells to a greater extent than normal bone marrow cells. Prior clinical studies demonstrated a sustained drug ratio and exposure in vivo and prolonged survival versus standard-of-care cytarabine plus daunorubicin chemotherapy (7+3 regimen) in older patients with newly diagnosed secondary acute myeloid leukemia (sAML). Patients and Methods In this open-label, randomized, phase III trial, 309 patients age 60 to 75 years with newly diagnosed high-risk/sAML received one to two induction cycles of CPX-351 or 7+3 followed by consolidation therapy with a similar regimen. The primary end point was overall survival. Results CPX-351 significantly improved median overall survival versus 7+3 (9.56 v 5.95 months; hazard ratio, 0.69; 95% CI, 0.52 to 0.90; one-sided P = .003). Overall remission rate was also significantly higher with CPX-351 versus 7+3 (47.7% v 33.3%; two-sided P = .016). Improved outcomes were observed across age-groups and AML subtypes. The incidences of nonhematologic adverse events were comparable between arms, despite a longer treatment phase and prolonged time to neutrophil and platelet count recovery with CPX-351. Early mortality rates with CPX-351 and 7+3 were 5.9% and 10.6% (two-sided P = .149) through day 30 and 13.7% and 21.2% (two-sided P = .097) through day 60. Conclusion CPX-351 treatment is associated with significantly longer survival compared with conventional 7+3 in older adults with newly diagnosed sAML. The safety profile of CPX-351 was similar to that of conventional 7+3 therapy.

scholarly journals Utilization of initial chemotherapy for newly diagnosed acute myeloid leukemia in the United States

2018 ◽  
Vol 2 (11) ◽  
pp. 1277-1282 ◽  
Author(s):  
Vijaya Raj Bhatt ◽  
Valerie Shostrom ◽  
Krishna Gundabolu ◽  
James O. Armitage
Keyword(s):  
United States ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
The United States ◽  
Insurance Status ◽  
Newly Diagnosed ◽  
Key Points ◽  
Facility Type ◽  
Acute Myeloid

Key Points An analysis of 61 775 adults with AML diagnosed between 2003 and 2011 demonstrated that 25% did not receive any chemotherapy. Factors such as facility type, patients’ race, income, and insurance status were associated with the rates of use of chemotherapy.

Expression of Phosphorylated Signal Transducer and Activator of Transcription 5 (pSTAT5) Is Associated with An Increased Risk of Death In Acute Myeloid Leukemia.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1675-1675
Author(s):  
Anna Brady ◽  
Sarah Gibson ◽  
Lisa Rybicki ◽  
Eric Hsi ◽  
Edward Copelan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Myeloid Leukemia ◽  
Signal Transducer ◽  
Newly Diagnosed ◽  
Risk Of Death ◽  
Increased Risk ◽  
History Of ◽  
Acute Myeloid

Abstract Abstract 1675 Background: Acute myeloid leukemia (AML) is characterized by rapid growth, resistance to therapy, and poor overall survival. Clinical and biologic prognostic markers can help define pathogenesis, guide treatment, and identify novel therapies. Phosphorylated signal transducer and activator of transcription 5 (pSTAT5) is one such potential marker. The transcription factor STAT5 regulates many aspects of cell growth, survival, and differentiation. Constitutive activation of STAT5 (by phosphorylation) has been identified in a number of malignancies, including AML. We investigated whether the level of pSTAT5 expression correlates with complete remission (CR) rates, progression-free survival (PFS), and overall survival (OS) in patients (pts) with newly diagnosed AML. Methods: From 1999 to 2005, all adult pts with newly diagnosed AML (WHO criteria) receiving induction chemotherapy and with an available diagnostic bone marrow biopsy performed at our institution were evaluated. B5-fixed bone marrow core biopsies were reviewed for areas with the highest concentration of blasts. A tissue microarray was constructed using 1 mm cores. The cores were arrayed in duplicate in the majority of samples. Immunohistochemistry was performed for pSTAT5 with anti-pSTAT5 a/b Y695/99 mouse monoclonal antibody (AX1; Advantex Bioreagents) using automated stainers and heat-induced epitope retrieval. In each case, five hundred blasts were counted. The percentage of cells staining positive for pSTAT5 expression was determined by a pathologist blinded to clinical results. Standard metaphase karyotypes were classified into cytogenetic (CG) risk groups by CALGB criteria. Cox proportional hazards analysis was used to identify univariate and multivariate prognostic factors for CR, PFS, and OS, including age at diagnosis, history of an antecedent hematologic disorder (AHD), WBC at diagnosis, pSTAT5 expression, and CG risk group. Results: Adequate tissue and clinical data were available in 112 pts. The median age was 57 years, and median WBC at diagnosis 12.0 K/ μL. Twenty six percent of pts had favorable CG, 41% intermediate risk, 27% high risk, and 6% other (unknown or could not be classified). Nineteen percent of pts had an AHD. pSTAT5 expression was absent in 58% of pts. The remainder of the pts had: 1–5% pSTAT5 (25% of pts), 10% pSTAT5 (11% of pts), 20% pSTAT5 (4% of pts), 30% pSTAT5 (1% of pts), and 50% pSTAT5 (2% of pts). Seventy percent of all pts achieved a CR following induction chemotherapy. Sixty-four percent of pts received post-remission chemotherapy, 3.6% an autologous transplant, and 13.6% an allogeneic transplant in first CR. Median PFS and OS were 9.6 months and 16.0 months, respectively. On univariate analysis, age, history of AHD, WBC at diagnosis, CG risk, and any pSTAT5 expression were prognostic factors for PFS and OS. In multivariable analyses controlling for the above prognostic factors, pSTAT5 expression > 0 was also significantly associated with an increased risk of death (HR 1.96, 95% CI 1.19–3.23, p=0.008), progression or death (HR 1.64, 95% CI 1.01–2.66, p=0.046), and relapse after achieving CR (HR 2.31, 95% CI 1.16–4.63, p=0.018). pSTAT5 expression was not a predictor of achievement of CR. Conclusions: pSTAT5 expression in newly diagnosed adults with AML is associated with a decreased PFS, decreased OS, and increased risk of relapse. Validation of its prognostic value requires additional study. Agents targeting this signaling pathway might improve the outcome of pts with AML. Disclosures: No relevant conflicts of interest to declare.

Phase I Study of Clofarabine (JC0707) in Adult Japanese Patients with Acute Myeloid Leukemia (AML)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4295-4295
Author(s):  
Takahiro Yamauchi ◽  
Tatsuya Suzuki ◽  
Kiyoshi Ando ◽  
Tadashi Nagai ◽  
Kazuhiko Kakihana ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Phase I ◽  
Myeloid Leukemia ◽  
The United States ◽  
World Health ◽  
Plasma Samples ◽  
Newly Diagnosed ◽  
The Us ◽  
Grade 3 ◽  
Acute Myeloid

Abstract Abstract 4295 Background and Purpose: Although cytarabine plus anthracycline (7+3 or 7+5) regimens are commonly used for induction therapy in patients (pts) with acute myeloid leukemia (AML) and there have been improvements in the treatment of AML in younger adults, there is no standard of care in pts with relapsed or refractory (R/R) AML. Treatment options for older pts and those with R/R disease remain limited. Clofarabine (JC0707) is a purine nucleoside analog approved in the United States (US) and European Union for the treatment of pediatric pts with R/R acute lymphocytic leukemia (ALL). In a phase II study from the US, single-agent clofarabine showed activity and acceptable toxicity in pts ≥ 60 years with untreated AML and adverse prognostic factors (Kantarjian, J Clin Oncol 2010;28:549–55). The purpose of this phase I open-label, multi-center study is to assess the safety, tolerability, and pharmacokinetics of clofarabine monotherapy in elderly Japanese pts with newly diagnosed AML for whom standard induction chemotherapy is unlikely to be of benefit or Japanese adult pts with R/R AML. Method: Adult pts (20–74 years) with R/R AML according to World Health Organization (WHO) criteria and elderly pts (60–74 years) with newly diagnosed AML were eligible to participate. Additional inclusion criteria included Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 and no prior hematopoietic stem cell transplant. The study utilized a standard 3 + 3 dose escalation method; 3 pts enrolled in each dosing cohort, 3 additional pts were added to cohorts where dose-limiting toxicities (DLTs) were observed. The maximum tolerated dose (MTD) was defined as the dose level below that for which 2 DLTs were observed. Based on prior clinical trials in the US, pts were to be treated with clofarabine 20 mg/m2/day (IV over 1 hr), 30 mg/m2/day, or 40 mg/m2/day for one 5 day cycle in cohorts 1, 2 and 3, respectively. Pts with evidence of hematologic response after one cycle could receive up to a maximum of 3 cycles. The primary endpoints of this study were MTD, safety, and pharmacokinetic (PK) parameters. Result: Until June 2011, 14 pts were enrolled and treated in this trial: cohort 1 (n=3), cohort 2 (n=6), and cohort 3 (n=5). Bioanalytical determination of clofarabine concentrations in plasma samples showed an increased concentration with increased dosage. No DLTs were noted in cohort 1 (20 mg/m2). Among the first 3 pts in cohort 2 (30 mg/m2), only 1 patient experienced DLT (reversible, grade 4 elevated ALT). Additionally, 2 pts in cohort 3 (40 mg/m2) experienced DLTs (grade 3 elevated ALT [n=1]; grade 3 elevated amylase [n=1]). Thus, the MTD was determined to be 30 mg/m2. Preliminary safety and efficacy data are available for 9 of these pts and presented herein. Overall, the most common all cause, non-hematologic toxicities were nausea and headache (89% each), rash and elevated ALT and AST (78% each), malaise (56%), pneumonia and hypokalemia (44% each), and elevated bilirubin and vomiting (33% each). Grade 3 or 4 toxicities were primarily hematologic and infectious occurring in 89% and 67% of patients, respectively. Only one patient developed a treatment-related serious adverse event (SAE) (herpes zoster). There were no AE related deaths and no patients discontinued therapy as a result of an AE. Two patients achieved complete remission (CR) and 2 patients achieved CR without platelet recovery (CRp), for an overall response rate (ORR) of 44% (Table 1). Additionally, plasma samples were obtained from all patients for PK evaluation; plasma concentration data from all 14 patients will be presented. Conclusion: Clofarabine monotherapy was well tolerated at doses up to 30mg/m2 and showed preliminary evidence of activity with 44% ORR in elderly newly diagnosed AML or adult Japanese pts with R/R AML, warranting further investigations. Disclosures: Off Label Use: Clofarabine (JC0707) is an investigational agent in Japan; this abstract assesses its use in adult AML patients. Ewesuedo:Sanofi Oncology: Employment. Tabata:Genzyme (a Sanofi company): Employment.

Hematopoietic Stem Cell Transplantation (HSCT) Benefits the Survival of Acute Myeloid Leukemia (AML) Patients with IDH1, NRAS and DNMT3A Mutations

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1981-1981
Author(s):  
Yang Xu ◽  
Zhen Yang ◽  
Hong Tian ◽  
Huiying Qiu ◽  
Aining Sun ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Gene Mutations ◽  
Newly Diagnosed ◽  
Hematopoietic Stem ◽  
Acute Myeloid

Abstract Abstract 1981 Background: Gene mutations may serve as potential markers to extend the prognostic parameters in acute myeloid leukemia (AML) patients. In this study, we detected distribution of mutations in the nucleophosmin gene (NPM1), C-KIT, the fms-related tyrosine kinase 3 gene (FLT3), Isocitrate dehydrogenase gene 1 and 2 (IDH1, IDH2), the neuroblastoma RAS viral oncogene homolog (NRAS) and DNA methyltransferase 3A gene (DNMT3A) in 442 newly diagnosed AML patients (none-APL). Associations of gene mutations with clinical outcomes in these patients followed HSCT treatment or chemotherapy were further evaluated. Methods: Between February 2005 and December 2011, 442 newly diagnosed AML (none-APL) patients in our centre were retrospectively analyzed. There are 248 males and 194 females, and the median ages were 40 (16–60) years. 393 patients (88.9%) of patients were with single or normal karyotype and 49 patients (11.1%) were with complex abnormal karyotype. In addition to MICM examination, direct sequencing was employed to access the distribution of mutations in of FLT3-ITD (exon14), FLT3-TKD (exon 20), NPM1 (exon12), C-KIT (exon8, 17), IDH2 (exon 4), NRAS (exon1, 2), DNMT3A (exon23) of 445 AML patients. Complete remission (CR) was achieved in 258 patients (58.4%) followed the standard induction therapy, 128 patients received HSCT (Allo-HSCT: 121 vs. Auto-HSCT: 7) therapy after first remission or second remission while 258 patients received consolidation chemotherapy contained 4–6 cycles high dose Ara-C (HD-Ara-C). Overall survival (OS) and Event-free survival (EFS) were measured at last follow-up (censored), and Kaplan-Meier analysis was used to calculate the distribution of OS and EFS. Results: In 442 AML (None-APL) patients, 44 patients (9.7%) had C-KIT mutations, 97 patients (21.9%) had NPM1 mutations, 95 patients (21.5%) had FLT3-ITD mutations, 26 patients (5.9%) had FLT3-TKD mutations, 23 patients (5.2%) had IDH1 mutations, 48 patients (10.9%) had IDH2 mutations, 31 patients (7.0%) had DNMT3A mutations, and 40 patients (9.0%) had NRAS mutations. Using COX regression, we found that mutations in FLT3-ITD (HR:2.113; 95%CI: 1.1420 to 3.144),IDH1 (HR:3.023; 95%CI: 1.055 to 3.879), NRAS (HR:1.881; 95%CI: 1.021 to 2.945), and DNMT3A (HR: 2.394; 95%CI: 1.328 to 4.315) were independent unfavorable prognostic indicators of overall survival of AML patients. We further compared the outcomes of AML patients with such gene mutations followed different therapy (HSCT vs. HD Ara-C), and results shown that patients with mutations in IDH1, NRAS and DNMT3A received HSCT therapy had better survival. The median OS and EFS of patients with FLT3-ITD, IDH1, NRAS and DNMT3A in the two groups (HSCT vs. HD Ara-C) were as follows: IDH1 (OS: 35 months vs. 11 months, p=0.016; EFS: 34 months vs. 8 months, p=0.012), NRAS (OS: 27months vs. 8 months, p=0.008; EFS: 23 months vs. 4 months, p=0.049), DNMT3A (OS: 66 months vs. 19 months, p=0.008; EFS: 54 months vs. 13 months, p=0.002). Conclusions: Taken together, our data proved that mutant FLT3-ITD, IDH1, NRAS, and DNMT3A might serve as poor prognostic markers and hematopoietic stem cell transplantation as first-line treatment could favor the outcome of AML patients carrying IDH1, NRAS, and DNMT3A mutations. Disclosures: No relevant conflicts of interest to declare.

Daunorubicine, Cytarabine and Cladribine (DAC) Vs Daunorubicine and Cytarabine (DA) Induction Treatment in Elderly Acute Myeloid Leukemia (AML) Patients – Results of the Prospective, Multicenter, Randomized Trial of the Polish Adult Leukemia Group (PALG)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3602-3602
Author(s):  
Agnieszka Pluta ◽  
Tadeusz Robak ◽  
Agata Wrzesien-Kus ◽  
Bozena Katarzyna Budziszewska ◽  
Kazimierz Sulek ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Treatment Option ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
Hematological Toxicity ◽  
Proportional Hazard ◽  
Newly Diagnosed ◽  
Acute Myeloid

Abstract Abstract 3602 Background: AML in elderly patients is associated with very poor prognosis. The best treatment option for this group of patients is not established, yet. The intensity of treatment depends on performance status and comorbidities. The previous PALG AML study showed that addition of cladribine (2CdA) to conventional induction therapy; especially in patients above 40 yrs, is associated with better outcome (Ho3owiecki 2004). Based on this observation we designed a study addressed to newly diagnosed AML patients above 60 yrs old, who were fit enough to intensive treatment. Aim: To verify whether addition of 2CdA has an impact to clinical outcome in newly diagnosed AML patients older than 60 years old. Methods: From October 2004 to November 2011, 178 patients from 16 hematological PALG centers were randomly assigned to DA induction therapy consisting of daunorubicine (DNR) 45mg/m2, intravenously (iv), day 1–3 and cytarabine (AraC) 100 mg/m2, iv, day 1–7 (DA) or DA with addition of 2CdA 5mg/m2, iv, day 1–5 (DAC). Patients, who achieved complete remission (CR), received one course of consolidation with mitoxantron 6mg/m2 iv day1–2 and AraC 100mg/m2 iv day 1–5, followed by six cycles of maintenance consisting of (DNR 30mg/m2 iv day 1–2 with AraC 100mg/m2 sc day 1–5 and tioguanine 100mg/m2, p.o., twice day, day 1–5 with AraC 100mg/m2 s.c. day 1–5, alternately). Response criteria were determined according to revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia (Chesson 2003). Statistical analysis: Pairwise comparisons between patient characteristics were performed by the Mann-Whitney U-test for continuous variables and by χ2-statistics or Fisher's exact test for categorical variable. The Kaplan-Meier estimates of survival were calculated and compared using the log-rank test. For multivariate analysis, the Cox proportional hazard regression model was applied. P values < 0.05 were considered significant. Results: 88 pts with median age 66 yrs (range 60–79 yrs) were randomized to DA and 90 pts with median age 64 yrs (range 60–79 yrs) was enrolled to DAC schema. The both groups were comparable in terms of age, sex, performance status, white blood cell count, hemoglobin level, platelets count, tumor burden parameters, cytogenetic, between the both groups. The overall CR rate was 38%. In DA and DAC groups CR was achieved in 33% and 43% pts, respectively (p=0.12). However, in patients under 65 yrs the trend towards higher CR rate in DAC arm than DA group was observed (47% vs. 29%, p=0.09). In pts above 65 yrs the CR rate was comparable (39% vs. 38%, p=0.8). The efficacy and hematological toxicity in DA and DAC groups was similar (Table 1). Also no statistical significant differences in non-hematological toxicity were observed (data not shown). Early deaths in DA and DAC did not differ significantly. Median overall survival (OS) in DA and DAC arm was also similar in both groups (Table 1). In proportional hazard Cox analysis only age under 65yo, CR achievement and WBC above 100G/L were important for better OS (p=0.02, p<0.001 and p=0.09). The presence of dysplastic changes, karyotype, LDH, number of bone marrow blasts did not influenced OS. Conclusions: Our data suggest that prolonged overall survival can be achieved in elderly AML patients mainly till 65yrs. Intensive therapy, especially in patients older than 65yrs, may be associated with high number of complications what results withdrawing from intensive treatment protocol. Hematological and non-hematological toxicity of DA and DAC schema is comparable, however higher CR rate in DAC group in patient till 65yrs may suggest, that addition of 2CdA to DA does not increase toxicity and may be a treatment option in this patient population. Disclosures: Wiktor-Jedrzejczak: Janssen-Cilag: Consultancy; Amgen: Consultancy; Novartis: Consultancy, Speakers Bureau; Pfizer: Consultancy; Bayer: Consultancy; Genopharm: Speakers Bureau; Celgene: Speakers Bureau; Genzyme: Speakers Bureau; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Real-World Outcomes Among Elderly Acute Myeloid Leukemia Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2271-2271
Author(s):  
Bruno C Medeiros ◽  
Sacha Satram-Hoang ◽  
Khang Q. Hoang ◽  
Faiyaz Momin ◽  
Deborah Hurst ◽  
...  
Keyword(s):  
Overall Survival ◽  
Real World ◽  
Lower Risk ◽  
Survival Benefit ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem ◽  
Risk Of Death ◽  
Age Cohort ◽  
Acute Myeloid

Abstract Introduction: The incidence of acute myeloid leukemia (AML) increases with age, however treatment efficacy and tolerability in older patients are poor compared to younger patients. Without treatment, patients succumb to their illness within a few months of diagnosis. Further, disease relapse is inevitable in the majority of cases without additional post-remission therapy after successful induction of remission. The use of allogeneic hematopoietic stem cell transplantation (HSCT) is considered a potential cure for AML but its use is limited in older patients because of significant comorbidities and increased transplant-related morbidity and mortality. This retrospective study assessed outcomes of older AML patients treated with chemotherapy with or without HSCT. Methods: The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database, was utilized in this retrospective cohort analysis of 3327 first primary AML patients. Patients were diagnosed between January 1, 2000 to December 31, 2009, were >66 years, continuously enrolled in Medicare Part A and B with no HMO coverage in the year prior to diagnosis and received treatment with chemotherapy with or without HSCT. Chi-square test for categorical variables and ANOVA or t-test for continuous variables was used to compare patient characteristics between treated patients with and without HSCT. Kaplan-Meier curves and Cox proportional hazards regression assessed overall survival. Date of last follow-up was December 31, 2010. Results: There were 276 (8%) patients who underwent HSCT therapy and 3051 (92%) who did not. HSCT patients were younger at diagnosis with mean age of 73 compared to the non-HSCT group (75 years; p<.0001). Seventy percent of HSCT patients compared to 55% of non-HSCT patients were under the age of 75 at diagnosis. HSCT patients were also more likely to be male. There were no statistical differences in comorbidity burden, poor performance indicators (PPI) or prior myelodysplastic syndrome (MDS) between both groups. The unadjusted median overall survival was higher for HSCT (9.7 months) compared to the non-HSCT group (4.7 months; log rank p=<0.0001). In multivariate survival analysis, patients who underwent HSCT had a 20% lower risk of death compared to those who did not receive HSCT (Table 1). Increasing age, male gender, increasing comorbidity score, prior MDS and PPI were significantly associated with higher risks of mortality. In a subset analysis stratified by age, the survival benefit with HSCT was only demonstrated in the younger age cohort ≤75 years old, and no difference in mortality risks were noted in the older age cohort >75 years (Table 1). Conclusions: In this real-world analysis of elderly AML patients treated in community oncology practice, only 8% of patients receiving chemotherapy underwent subsequent HSCT therapy. Chronologic age appears to be the driving factor in receiving HSCT. HSCT therapy was associated with a 20% lower risk of death compared to patients receiving chemotherapy only and the survival benefit was more pronounced among the younger cohort, age ≤75 years with a 36% reduction in mortality risk. These findings provide further insight into disease management and provide an important context for identifying opportunities to improve the quality of treatment strategies in the real world setting. Table 1: Multivariate Overall Survival Analysis HSCT All (N=3327) ≤ 75 (n=1857) >75 years (n=1470) HR 95% CI HR 95% CI HR 95% CI No ref ref ref Yes 0.80 0.69-0.92 0.63 0.53-0.75 1.22 0.97-1.54 Disclosures Satram-Hoang: Genentech, Inc.: Consultancy. Hurst:Genentech, Inc.: Employment. Reyes:Genentech, Inc.: Employment.

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