Big Data Analysis of Treatment Patterns and Outcomes Among Elderly Medicare Acute Myeloid Leukemia Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3698-3698 ◽  
Author(s):  
Sacha Satram-Hoang ◽  
Carolina Reyes ◽  
Khang Q. Hoang ◽  
Faiyaz Momin ◽  
Deborah Hurst ◽  
...  
Keyword(s):  
Overall Survival ◽  
Performance Indicators ◽  
Myeloid Leukemia ◽  
Poor Performance ◽  
Patient Characteristics ◽  
Multivariate Survival Analysis ◽  
Comorbidity Score ◽  
Multivariate Survival ◽  
Elderly Aml ◽  
Acute Myeloid

Abstract Introduction: Acute myeloid leukemia (AML) is the most common acute leukemia in adults with a median age at diagnosis of 66 years. Over half of the patients are diagnosed at age 65 or older and have shown no improvement in outcomes compared to younger patients in last few decades. The goal of the study was to examine the patient characteristics associated with receiving treatment and the survival outcomes in an older population in routine clinical practice. Methods: This retrospective cohort analysis utilized data from the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. The database is a nationally representative collection of Medicare patients in 18 population-based SEER cancer registries from diverse geographic areas representative of about 26% of the United States population. The analysis included 8336 first primary AML patients diagnosed between January 1, 2000 to December 31, 2009, >66 years, and continuously enrolled in Medicare Part A and B with no HMO coverage in the year prior to diagnosis. Chi-square test for categorical variables and ANOVA or t-test for continuous variables was used to assess differences in patient and disease related characteristics by treatment status. Kaplan-Meier curves and Cox proportional hazards regression assessed survival by treatment status adjusting for age, sex, race, prior myelodysplastic syndrome (MDS), poor performance indicators (PPI), comorbidity, income, education, marital status, year of diagnosis and geographic region. Logistic regression modelling assessed patient characteristics predictive of not receiving treatment. Results: There were 3327 (40%) patients who received treatment with chemotherapy within 3 months of diagnosis and 5009 (60%) patients who did not receive treatment. Treatment rates increased over the study time-period from 35% in the year 2000 to 50% in 2009 (p<.0001). Treated patients were younger (75 vs. 81 years), more likely male (55% vs. 50%), married (61% vs. 47%), lower incidence of antecedent hematologic malignancy (15% vs. 19% prior MDS), less likely to have poor performance indicators (7% vs. 17%) and had lower comorbidity score (p<.0001) than untreated patients. In the treated cohort, 57%, 25%, 10% and 8% had NCI comorbidity score of 0, 1, 2, and ≥3 respectively. In the untreated cohort, 47%, 25%, 14% and 14% had NCI comorbidity score of 0, 1, 2, and ≥3 respectively. The most common comorbidities were hypertension (51%), hyperlipidemia (33%), coronary artery disease (25%), diabetes (21%), and atrial fibrillation (19%). In the logistic regression analysis, increasing age, increasing comorbidity score, black race, prior MDS and PPI were shown to significantly decrease the likelihood of receiving treatment. The median unadjusted overall survival was 2.5 months for the overall population and was longer for treated patients (6.1 months) compared to untreated patients (1.5 months; log rank p <.0001; Figure 1). In multivariate survival analysis, treated patients exhibited a 43% lower risk of death compared to untreated patients (HR=0.57; 95% CI=0.54-0.60). Increasing age, increasing comorbidity score and PPI were significantly associated with higher mortality risks. Conclusions: Although therapy use has increased over time, this large observational study showed that about 60% of elderly AML patients remain untreated following diagnosis. In the multivariate survival analysis, use of anti-leukemic therapy was associated with significant survival benefit in this cohort of patients. These results suggest an opportunity to improve treatment strategies and delivery to optimize patient outcomes in elderly AML patients. Figure 1: Unadjusted Overall Survival Figure 1:. Unadjusted Overall Survival Disclosures Satram-Hoang: Genentech, Inc.: Consultancy. Reyes:Genentech, Inc.: Employment. Hurst:Genentech, Inc.: Employment.

Comparative Effectiveness of Chemotherapy in an Elderly Acute Myeloid Leukemia Population in the United States

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2272-2272 ◽  
Author(s):  
Bruno C Medeiros ◽  
Sacha Satram-Hoang ◽  
Khang Q. Hoang ◽  
Faiyaz Momin ◽  
Deborah Hurst ◽  
...  
Keyword(s):  
Overall Survival ◽  
Elderly Patients ◽  
Performance Indicators ◽  
Survival Benefit ◽  
Myeloid Leukemia ◽  
Poor Performance ◽  
Comorbidity Score ◽  
Elderly Aml ◽  
Comorbidity Burden ◽  
Acute Myeloid

Abstract Introduction: A disproportionate number of newly diagnosed acute myeloid leukemia (AML) occurs in elderly patients. Conventional chemotherapy treatments for AML may be highly toxic and elderly patients often have increased comorbidity burden and loss of organ reserve that may impact their ability to tolerate therapy. Consequently, fewer than half of elderly patients with AML receive anti-leukemic therapy and outcomes among these patients have not improved in the last few decades. We described treatment patterns and outcomes of elderly AML patients in a real-world population. Methods: We utilized a retrospective cohort analysis of first primary AML patients in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Patients were diagnosed between January 1, 2000 to December 31, 2009, >66 years, and continuously enrolled in Medicare Part A and B in the year prior to diagnosis. There were 8336 patients identified, of which 5009 (60%) did not receive treatment (NT). Chemotherapy agent definition was not possible in approximately 70% of patients who received therapy because chemotherapy was administered during inpatient stays which are paid based on ICD-9 diagnosis or procedures codes only and not chemotherapy codes. Of those initiating treatment within 3 months after diagnosis, 345 were treated with azacitidine + decitabine (AD) and 124 were treated with cytarabine+anthracycline (CA). Statistical comparisons were made between NT, AD and CA. To compare demographic and clinical characteristics by treatment, the Chi-square test for categorical variables and ANOVA or t-test for continuous variables was used. Kaplan-Meier curves and corresponding log-rank test were used to compare overall survival by treatment. Cox regression and propensity-weighted analyses estimated the relative risk of death adjusting for demographic and clinical factors. The date of last follow-up was December 31, 2010. Results: Patients receiving CA were younger (mean age 73 vs. 78 and 81), more likely male (62% vs. 59% and 50%), married (71% vs. 61% and 47%), had less secondary AML (7% vs. 21% and 19% with prior myelodysplastic syndrome [MDS]), less likely to have poor performance indicators (2% vs. 9% and 17%) and had lower comorbidity score compared to those receiving AD and NT, respectively. Similarities in age, comorbidity burden and proportion with high risk disease were noted in AD and NT patients. The median unadjusted overall survival was longer for patients treated with CA (18.9 months) compared to AD (6.6 months) and NT (1.7 months; log rank p <.0001). After adjusting for all covariates in the survival model, a 69% reduction in mortality was observed among patients treated with CA and a 53% reduction in mortality was observed among patients treated with AD, compared to those who did not receive any treatment (Table 1). The survival benefit of AD and CA were maintained in the younger (≤75) and older (>75) cohorts. Increasing age, increasing comorbidity score and presence of poor performance indicators were associated with significant increases in mortality. Propensity score adjusted multivariate analysis demonstrated similar risk reductions for CA (HR=0.41; 95% CI=0.34-0.49) and AD (HR=0.49; 95% CI=0.44-0.55). Conclusions: A substantial proportion of elderly AML patients are not receiving therapy for their disease. We observed a significant survival benefit with receiving treatment, even among the AD group who had similar characteristics to the NT group. Further, improved survival after receiving CA compared to AD was noted, but the propensity score adjusted analysis demonstrated similar reductions in death. The findings from this study can provide an important baseline for evaluating the benefits of new treatments under investigation. Table 1 Multivariate Overall Survival Analysis Covariates* n HR 95% CI Treatment Not Treated 5009 ref AD 345 0.47 0.42-0.53 CA 124 0.31 0.25-0.39 Age 66-70 537 ref 71-75 920 1.31 1.17-1.46 76-80 1276 1.42 1.27-1.58 >80 2745 1.68 1.52-1.86 Poor Performance Indicators No 4605 ref Yes 873 1.30 1.20-1.41 *Model also includes sex, race, comorbidity score, prior MDS, marital status, and geographic region Disclosures Satram-Hoang: Genentech, Inc.: Consultancy. Hurst:Genentech, Inc.: Employment. Reyes:Genentech, Inc.: Employment.

scholarly journals Elderly AML: A Five-Year Retrospective Review on Prognostic Features

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5187-5187
Author(s):  
Akshay Amaraneni ◽  
Jennifer Segar ◽  
Trace Bartels ◽  
Onyemaechi Okolo ◽  
Andrew C Rettew ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Acute Myeloid Leukemia ◽  
Retrospective Review ◽  
Myeloid Leukemia ◽  
Small Sample Size ◽  
Small Sample ◽  
Risk Category ◽  
Elderly Aml ◽  
Acute Myeloid

Abstract Background: Acute Myeloid Leukemia (AML) is a disease of the elderly with a median age of diagnosis of 70 years. Prognosis in this age group is poor, with median overall survival of those undergoing treatment ranging from seven to twelve months. Treatment is difficult for a variety of reasons, including - higher incidence of co-morbid conditions (including frailty and decline in functional status), decreased ability to tolerate infections, socioeconomic considerations, and more aggressive disease phenotype. We present a single-institution retrospective review of acute myeloid leukemia outcomes with respect to these and other variables. Methods: A retrospective chart review was performed on all patients with a new diagnosis of AML from November 2013 through October 2017. Descriptive statistics were performed using excel, inferential statistics including Kaplan-Meier with comparison of survival curves by Logrank test and Cox-proportional hazard regression analysis, and correlation coefficients were performed using MEDCALC statistical software package. Results: Eighty-four AML patients in total were diagnosed with acute myeloid leukemia within the specified time frame, of these, 45 patients were age 65 or older (elderly) and were included in further analysis. Median age of elderly AML patients in this study was 70 years. Six of these patients were diagnosed with secondary AML (having arisen from MDS (N = 4), or other hematologic malignancy (N=2), and two had therapy-related AML. Eight patients had favorable risk disease, 13 intermediate risk, and 24 adverse risk according to ELN 2017 criteria. The median survival of all elderly patients was 322 days. Median survival of elderly AML according to ELN 2017 risk category criteria (Favorable, Intermediate, or Poor) was not reached (mean 880 days), 390 days, and 117 days, respectively (p = 0.0368 by cox hazard regression). Survival was not affected by type of treatment (induction vs hypomethylating agent (HMA); median 579 and 166 days (p = 0.1378) and mean 1552 and 364 days, respectively. This is likely due to small sample size, although survival does appear to favor intensive induction. Survival was not affected by number of medical co-morbidities (p = 0.66), presence of infectious complications (p=0.152), or unplanned hospitalization (p = 0.144). Overall use of clinical trials (N=3) and transplant (N=2) were low, precluding meaningful statistical analysis. However, both patients undergoing transplant exceeded the median OS (579 and 4745 days). Median OS of patients identified as White/Caucasian was greater than those identified as Hispanic/Latino (166 days vs 66 days, respectively), this did not reach statistical significance. Conclusion: Given the limitations of a retrospective review and relatively small sample size, our data shows that the 2017 ELN risk category is the strongest predictor of overall survival. Statistically, those undergoing intensive induction did not have a longer overall survival than those treated with HMAs, highlighting the need for careful selection of induction therapy candidates, and the need for clinical trials investigating other less intense treatment options for patients in this category. Interestingly, number of medical co-morbidities did not influence overall survival, nor did unplanned hospitalizations, presence/absence of significant infections during therapy, or race/ethnicity. Our data suggest an under-utilization of clinical trials and allogeneic hematopoietic stem cell transplant, both of which may serve to improve prognosis. Disclosures No relevant conflicts of interest to declare.

Which Patient Characteristics Impact Treatment Choice in Elderly Patients with Chronic Lymphocytic Leukemia?

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 967-967
Author(s):  
Sacha Satram-Hoang ◽  
Carolina Reyes ◽  
Khang Hoang ◽  
Faiyaz Momin ◽  
Sridhar R Guduru ◽  
...  
Keyword(s):  
Overall Survival ◽  
Patient Characteristics ◽  
Lymphocytic Leukemia ◽  
Multivariate Survival Analysis ◽  
Treatment Groups ◽  
Risk Of Death ◽  
Multivariate Survival ◽  
Time Period ◽  
Stage Disease ◽  
Comorbidity Burden

Abstract Abstract 967 Introduction: Therapy selection in chronic lymphocytic leukemia (CLL) patients is based on the severity of the disease as well as patient characteristics such as age and comorbidity. National Comprehensive Cancer Network guidelines suggest that frail patients or those with significant comorbidity can be treated with oral chlorambucil (CLB) or single agent rituximab (R-mono). While treatment outcomes are mostly available from clinical trial data in younger patients, less is known about the effect of comorbidities on outcomes in elderly CLL patients in the real-world setting. Methods: The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database, was utilized in this retrospective cohort analysis of 3366 first primary CLL patients. Patients were diagnosed between January 1, 1998 to December 31, 2007, were >66 years, continuously enrolled in Medicare Part A and B with no HMO coverage in the year prior to diagnosis and received first-line treatment with any oral or infused therapy. CLB is covered by Medicare Part D and data for its use were only available from 2007–2009 in the SEER-Medicare dataset. The NCI comorbidity index, a widely used and validated measure of comorbidity in cancer patients was assessed using claims in the year prior to diagnosis for each patient. Kaplan-Meier curves and Cox proportional hazards regression assessed survival by treatment type. Date of last follow-up was December 2009. Results: There were 153 CLB, 606 R-mono, 702 R+IV Chemo, and 1905 IV Chemo-only patients. CLB and R-mono patients were older at diagnosis with mean age of 77 compared to R+IV Chemo (73 years) and IV Chemo-only (76 years; p<.0001). 31% of R-mono patients were over the age of 80 at diagnosis (Table 1). CLB patients were more likely to be female and non-white compared to the other treatment groups (Table 1). R-mono patients had a higher comorbidity burden and were diagnosed with more advanced stage disease compared to other treatment groups (Table 1). R-mono patients also had a significantly higher amount of pre-existing anemia (95% vs. 77–88%; p<.0001) and thrombocytopenia (81% vs. 48–72%; p=0.0184) compared to other treatment groups. In the multivariate survival analysis we compared CLB to R-mono during the time period 2007–2009 and R+IV Chemo to IV Chemo-only during the time period 1998–2009. The unadjusted overall survival was higher for R-mono compared to CLB (log rank p=0.0478). The unadjusted overall survival was higher for R+IV Chemo compared to IV Chemo-only (log rank p <.0001) with 5-year overall survival rates of 72% (SE=1.09) versus 52% (SE=1.03) respectively. In multivariate survival analysis, adjusting for age, sex, race, stage, comorbidity, income, diagnosis year and geographic region, IV Chemo-only patients had a 39% higher risk of death compared to R+IV Chemo patients (HR=1.39; 95% CI=1.18-1.62) and CLB patients had a non-significant 2-fold higher risk of death compared to R-mono patients (HR=2.27; 95%CI=0.96-5.38). Increasing age and increasing comorbidity score were significantly associated with higher risks of mortality. Conclusions: Patient characteristics such as age, comorbidity burden and gender appear to be important factors in prescribing treatment for CLL. R-mono patients were the oldest with more advanced stage disease at diagnosis and highest comorbidity burden while R+IV Chemo patients were the youngest with earlier stage disease and lowest comorbidity burden. R-containing regimens exhibited a greater survival benefit compared to oral or infused chemo-only regimens. Disclosures: Satram-Hoang: Genentech, Inc.: Consultancy. Reyes:Genentech, Inc.: Employment, Roche Stock Other. Skettino:Genentech, Inc. : Employment, Roche Stock Other.

A Randomized Trial Comparing Individualized Vs. Non-Individualized Treatment for Elderly Acute Myeloid Leukemia: JALSG GML200 Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2961-2961
Author(s):  
Atsushi Wakita ◽  
Shigeki Ohtake ◽  
Satoru Takada ◽  
Fumiharu Yagasaki ◽  
Hirokazu Komatsu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Survival Rate ◽  
Elderly Patients ◽  
Myeloid Leukemia ◽  
Bone Marrow Examination ◽  
Individualized Therapy ◽  
Elderly Aml ◽  
To Receive ◽  
Acute Myeloid

Abstract The outcome of elderly patients with acute myeloid leukemia (AML) has not been improved for these three decades, although the incidence is getting increased with the aging of the population in Japan. In the JALSG GML200 study, we prospectively registered all elderly patients with AML during this study irrespective of the eligible criteria,. Since elderly patients are less able to tolerate to intensive cyottoxic intensive chemotherapy, we conducted a randomized study to assess an individualized induction treatment. After consolidation chemotherapy, we evaluated the adjuvant effect of ubenimex (UBX), an anti-leukemia immunomodulator. Method: From April 2000 to August 2005, the JALSG GML200 study registered all newly diagnosed AML patients aged 65 years and over. Patients who satisfied the eligibility criteria were randomized to receive either the individualized therapy (arm B) or non-individualized therapy (arm A). Patients who were not eligible were classified in arm C. Induction therapy of Arm A: enocitabine (BH-AC) 200 mg/m2 on days 1–8, 3 h infusion + daunorubicin (DNR) 40 mg/m2 on days 1–3, 30 min infusion. Arm B: BH-AC 200 mg/m2 on days 1–8, with extension to day 12 according to the results of bone marrow examination on days 7 and 10, + DNR 40 mg/m2 on days 1–3, with extension on day 12 depending on the results of bone marrow examination on days 7 and 10. Patients who achieved a complete response (CR) were randomized again to receive immuno-therapy with ubenimex (group UY) or without ubenimex (group UN). Consolidation therapy consisted of three courses: BH-AC 200 mg/m2 on days 1–5 + Mitoxantrone (MIT) 7 mg/m2 on days 1–3, BH-AC 200 mg/m2 on days 1–5 + DNR 30 mg/m2 on days 1–2, ETP 100 mg/m2 on days 1–3, BH-AC 200 mg/m2 on days 1–5 + ACR 14 mg/m2 on days 1–5. Result: Of the 374 patients registered, 244 patients were eligible for randomization to arms A and B, and 235 patients were evaluable. The median patients’ age of arms A, B and C were 70 (range, 65–79), 71 (range, 65–79), and 74 years (range, 65–92), respectively. CR rate of arm A was 63.2% and that of arm B was 65.3% (p = 0.75). CR rates of male and female patients significantly differed in each arm (arm A: male 55.4% vs. female 76.3%, p=0.053, arm B: male 53.1% vs. female 80.0%, p=0.008). Overall survival rates at 3 years of arms A and B were 25.5% and 21.5% (p = 0.56), respectively. With reference to survival with or without ubenimex in patients who achieved CR, the overall survival rate at 3 years was 43.1% for arm UY and 26.9% for arm UN (p=0.073). The number of patients in arm C was 130, and most patients in this arm received similar induction chemotherapy using DNR and BH-AC. The survival rate of this group at 3 years was unexpectedly high at 29.4%. Conclusion: Induction chemotherapy using DNR and BH-AC is one of the superior methods to achieve CR in elderly AML patients. However, individualized treatment has little advantage over non-individualized therapy. The remission rate of the female patients is higher than male patients, and it may have relations with a long life span of the Japanese female. Long-term survival rate is still unfavorable and search for a better post-remission therapy is warranted. Immunomodulator therapy using ubenimex provides a possible benefit for longer survival in elderly AML patients at CR.

A Randomized Open-Label Study To Evaluate The Efficacy Of Azacitidine For Post-Remission Therapy Of Acute Myeloid Leukemia In Elderly Patients (QOLESS AZA-AMLE)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3967-3967
Author(s):  
Esther Natalie Oliva ◽  
Stella Santarone ◽  
Pietro Leoni ◽  
Caterina Alati ◽  
Antonio Volpe ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Best Supportive Care ◽  
Intensive Chemotherapy ◽  
Consolidation Chemotherapy ◽  
Open Label ◽  
Elderly Aml ◽  
Acute Myeloid

Abstract Background The incidence of acute myeloid leukemia (AML) increases with age. In elderly AML patients, intensive chemotherapy has been associated with complete remission (CR) rates of approximately 45%, considerably lower than in younger patients; the duration of remission is shorter and the early treatment-related mortality is high, 30% to 50%, which partially explains a median survival of 7 to 12 months. Several studies have suggested that maintenance therapy may improve CR duration and long-term, disease-free survival (DFS). Grovdal et al (2010) treated 60 elderly patients with high-risk myelodysplastic syndrome (MDS) or AML with cytarabine-based induction therapy resulting in CR in 24 patients who continued on to 5-Azacitidine (5-Aza) maintenance therapy. The median duration of complete response was 13.5 months. The median OS for the 5-Azacitidine-treated group was 20 months. Aims The present phase III, prospective, randomized, open-label, multicenter trial is designed to assess the efficacy of post-remission treatment with 5-Aza versus best supportive care in a cohort of subjects of > 60 years of age with AML, and in CR after conventional induction (“3+7”) and consolidation chemotherapy. Primary objectives are to evaluate overall survival overall survival and DFS at 2 years; secondary objectives are to evaluate the number and length of hospitalizations in the 2 arms in the 2-year post-remission period. Methods Approximately 95 patients with the following criteria: newly diagnosed AML with > 30% myeloid marrow blasts, either “de novo” or evolving from a MDS not previously treated with chemotherapeutic agents; no contraindications for intensive chemotherapy and performance status<3 will be included. Thirty-eight patients will be randomized in the post-remission phase 1:1. Standard induction chemotherapy consists of two courses of 3 + 7 with Daunorubicin at a daily dosage of 40 mg/m2 for 3 days (days 1-3) in combination with 100 mg/m2 cytarabine per day as a continuous IV infusion for 7 days (days 1-7). Consolidation consists of cytarabine 800 mg/m2 3 hour infusion bid (days 1-3). Patients in CR are randomized 1:1 to receive best supportive care (BSC) or 5-Aza according to the following schema: 50 mg/sqm s.c. or i.v. for 7 days every 28 days and increase after 1st cycle, if well tolerated, to 75 mg/m2 s.c or i.v. for 7 days (5 + weekend off + 2) every 28 days for further 5 cycles, followed by 6 cycles every 56 days for 2 years post-remission. Results At the time of the present report 58 patients have been included in the study. Median age at diagnosis was 72, interquartile range (IQR) 65-75 years, M/F 34/24. During induction-consolidation chemotherapy, 16 patients were relapsed/refractory, 9 patients died, 3 patients were excluded for protocol violation, 3 refused to continue and 8 have not yet reached consolidation treatment. Nineteen patients have been randomized; characteristics of patients are shown in the table. Eighteen patients have reached at least a 4 week follow-up. Amongst these, 11 patients are still in CR at a median observation time of 25.4, IQR 12.9-47.4 weeks. Five patients in the BSC arm have experienced AML recurrence at 7, 8, 13, 21, 49 weeks, respectively, verus 2 patients in the 5-Aza arm at 42 and 47 weeks. DFS is longer in the 5-Aza arm (Figure). Grade 3-4 adverse events included neutropenia in 2 cases in the 5-Aza arm and in 1 case in the BSC arm. There were no hospitalizations related to the adverse events in either arm. Conclusions Preliminary results suggest that in elderly AML patients receiving standard induction-consolidation chemotherapy, 5-Aza post-CR is well-tolerated and may prolong survival. Disclosures: Oliva: Celgene: Consultancy. Off Label Use: Azacitidine is indicated for the treatment of adult patients who are not eligible for haematopoietic stem cell transplantation with: • intermediate-2 and high-risk myelodysplastic syndromes (MDS) according to the International Prognostic Scoring System (IPSS), • chronic myelomonocytic leukaemia (CMML) with 10-29 % marrow blasts without myeloproliferative disorder, • acute myeloid leukaemia (AML) with 20-30 % blasts and multi-lineage dysplasia, according to World Health Organisation (WHO) classification.

Selection of Elderly Acute Myeloid Leukemia Patients for Intensive Chemotherapy: Effectiveness of Intensive Chemotherapy and Subgroup Analysis

2014 ◽  
Vol 133 (3) ◽  
pp. 300-309 ◽  
Author(s):  
Dae Sik Kim ◽  
Ka Won Kang ◽  
Eun Sang Yu ◽  
Hong Jun Kim ◽  
Jung Sun Kim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Subgroup Analysis ◽  
Myeloid Leukemia ◽  
Treatment Guideline ◽  
Definitive Treatment ◽  
Intensive Chemotherapy ◽  
Elderly Aml ◽  
Acute Myeloid

Background: Despite the advances in acute myeloid leukemia (AML) treatment, the prognosis of elderly patients remains poor and no definitive treatment guideline has been established. In the present study, we aimed to evaluate the effectiveness of intensive chemotherapy in elderly AML patients and to determine which subgroup of patients would be most responsive to the therapy. Methods: We retrospectively analyzed 84 elderly patients: 35, 19, and 30 patients were administered intensive chemotherapy, low-dose chemotherapy, and supportive care, respectively. Results: Among those who received intensive chemotherapy, there were 17 cases of remission after induction chemotherapy; treatment-related mortality was 22.9%. The median overall survival was 7.9 months. Multivariate analysis indicated that the significant prognostic factors for overall survival were performance status, fever before treatment, platelet count, blast count, cytogenetic risk category, and intensive chemotherapy. Subgroup analysis showed that intensive chemotherapy was markedly effective in the relatively younger patients (65-70 years) and those with de novo AML, better-to-intermediate cytogenetic risk, no fever before treatment, high albumin levels, and high lactate dehydrogenase levels. Conclusions: Elderly AML patients had better outcomes with intensive chemotherapy than with low-intensity chemotherapy. Thus, appropriate subgroup selection for intensive chemotherapy is likely to improve therapeutic outcome. © 2014 S. Karger AG, Basel

scholarly journals Comparative effectiveness of glasdegib versus venetoclax combined with low-dose cytarabine in acute myeloid leukemia

2021 ◽  
Author(s):  
Gabriel Tremblay ◽  
Patrick Daniele ◽  
Timothy Bell ◽  
Geoffrey Chan ◽  
Andrew Brown ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Comparative Effectiveness ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Patient Characteristics ◽  
Treatment Comparison ◽  
Transfusion Independence ◽  
Low Dose Cytarabine ◽  
Acute Myeloid

Background: Two combination therapies recently approved and recommended for use in combination with low-dose cytarabine (LDAC) in acute myeloid leukemia patients unfit for intensive chemotherapy are glasdegib+LDAC and venetoclax+LDAC. Materials & methods: An indirect treatment comparison used median overall survival, overall survival hazard ratios, complete remission (CR), CR+CR with incomplete blood count recovery and transfusion independence to assess comparative effectiveness, and a simulated treatment comparison accounted for differences in patient characteristics between trials. Results: Differences in efficacy between glasdegib+LDAC and venetoclax+LDAC were suggestive and not statistically significant. Conclusion: With no significant differences in comparative effectiveness, considerations such as safety profiles, burden of administration and patient preference are likely to guide treatment decisions.

Enasidenib: First Mutant IDH2 Inhibitor for the Treatment of Refractory and Relapsed Acute Myeloid Leukemia

2019 ◽  
Vol 18 (14) ◽  
pp. 1936-1951 ◽  
Author(s):  
Raghav Dogra ◽  
Rohit Bhatia ◽  
Ravi Shankar ◽  
Parveen Bansal ◽  
Ravindra K. Rawal
Keyword(s):  
Clinical Trial ◽  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Adverse Effects ◽  
Blood Cells ◽  
Myeloid Leukemia ◽  
White Blood Cells ◽  
Phase Iii ◽  
Acute Myeloid

Background: Acute myeloid leukemia is the collective name for different types of leukemias of myeloid origin affecting blood and bone marrow. The overproduction of immature myeloblasts (white blood cells) is the characteristic feature of AML, thus flooding the bone marrow and reducing its capacity to produce normal blood cells. USFDA on August 1, 2017, approved a drug named Enasidenib formerly known as AG-221 which is being marketed under the name Idhifa to treat R/R AML with IDH2 mutation. The present review depicts the broad profile of enasidenib including various aspects of chemistry, preclinical, clinical studies, pharmacokinetics, mode of action and toxicity studies. Methods: Various reports and research articles have been referred to summarize different aspects related to chemistry and pharmacokinetics of enasidenib. Clinical data was collected from various recently published clinical reports including clinical trial outcomes. Result: The various findings of enasidenib revealed that it has been designed to allosterically inhibit mutated IDH2 to treat R/R AML patients. It has also presented good safety and efficacy profile along with 9.3 months overall survival rates of patients in which disease has relapsed. The drug is still under study either in combination or solely to treat hematological malignancies. Molecular modeling studies revealed that enasidenib binds to its target through hydrophobic interaction and hydrogen bonding inside the binding pocket. Enasidenib is found to be associated with certain adverse effects like elevated bilirubin level, diarrhea, differentiation syndrome, decreased potassium and calcium levels, etc. Conclusion: Enasidenib or AG-221was introduced by FDA as an anticancer agent which was developed as a first in class, a selective allosteric inhibitor of the tumor target i.e. IDH2 for Relapsed or Refractory AML. Phase 1/2 clinical trial of Enasidenib resulted in the overall survival rate of 40.3% with CR of 19.3%. Phase III trial on the Enasidenib is still under process along with another trial to test its potency against other cell lines. Edasidenib is associated with certain adverse effects, which can be reduced by investigators by designing its newer derivatives on the basis of SAR studies. Hence, it may come in the light as a potent lead entity for anticancer treatment in the coming years.

AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations

Blood ◽  
2009 ◽  
Vol 114 (26) ◽  
pp. 5352-5361 ◽  
Author(s):  
Jih-Luh Tang ◽  
Hsin-An Hou ◽  
Chien-Yuan Chen ◽  
Chieh-Yu Liu ◽  
Wen-Chien Chou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Remission Rate ◽  
Adult Patients ◽  
Poor Prognostic Factor ◽  
The Impact ◽  
Runx1 Mutation ◽  
Acute Myeloid

AbstractSomatic mutation of the AML1/RUNX1(RUNX1) gene is seen in acute myeloid leukemia (AML) M0 subtype and in AML transformed from myelodysplastic syndrome, but the impact of this gene mutation on survival in AML patients remains unclear. In this study, we sought to determine the clinical implications of RUNX1 mutations in 470 adult patients with de novo non-M3 AML. Sixty-three distinct RUNX1 mutations were identified in 62 persons (13.2%); 32 were in N-terminal and 31, C-terminal. The RUNX1 mutation was closely associated with male sex, older age, lower lactic dehydrogenase value, French-American-British M0/M1 subtypes, and expression of HLA-DR and CD34, but inversely correlated with CD33, CD15, CD19, and CD56 expression. Furthermore, the mutation was positively associated with MLL/PTD but negatively associated with CEBPA and NPM1 mutations. AML patients with RUNX1 mutations had a significantly lower complete remission rate and shorter disease-free and overall survival than those without the mutation. Multivariate analysis demonstrated that RUNX1 mutation was an independent poor prognostic factor for overall survival. Sequential analysis in 133 patients revealed that none acquired novel RUNX1 mutations during clinical courses. Our findings provide evidence that RUNX1 mutations are associated with distinct biologic and clinical characteristics and poor prognosis in patients with de novo AML.

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