New Diagnosis Of Acute Myeloid Leukemia Research Articles

Home Time Among Older Adults With Acute Myeloid Leukemia Following Chemotherapy

Patients with acute myeloid leukemia (AML) recognize days spent at home (home time) vs in a hospital or nursing facility as an important factor in treatment decision making. No study has adequately described home time among older adults with AML. To describe home time among older adults with AML (aged ≥66 years) and compare home time between 2 common treatments: anthracycline-based chemotherapy and hypomethylating agents (HMAs). A cohort of adults aged 66 years or older with a new diagnosis of AML from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database in 2004 to 2016 was identified. Individuals were stratified into anthracycline-based therapy, HMAs, or chemotherapy, not otherwise specified (NOS) using claims. The primary outcome was home time, quantified by subtracting the total number of person-days spent in hospitals and nursing facilities from the number of person-days survived and dividing by total person-days. A weighted multinomial regression model with stabilized inverse probability of treatment weighting to estimate adjusted home time was used. The cohort included 7946 patients with AML: 2824 (35.5%) received anthracyclines, 2542 (32.0%) HMAs, and 2580 (32.5%) were classified as chemotherapy, NOS. Median (IQR) survival was 11.0 (5.0-27.0) months for those receiving anthracyclines and 8.0 (3.0-17.0) months for those receiving HMAs. Adjusted home time for all patients in the first year was 52.4%. Home time was highest among patients receiving HMAs (60.8%) followed by those receiving anthracyclines (51.9%). Despite having a shorter median survival, patients receiving HMAs had more total days at home and 33 more days at home in the first year on average than patients receiving anthracyclines (222 vs 189). This retrospective study of older adults with AML using SEER-Medicare data and propensity score weighting suggests that the additional survival afforded by receiving anthracycline-based therapy was entirely offset by admission to the hospital or to nursing facilities.

Association of Fried’s frailty phenotype, but not the clinical frailty scale, with overall survival in older adults with acute myeloid leukemia.

e23222 Background: Frailty is a geriatric syndrome marked by increased vulnerability to stressors. “Fitness,” is utilized to guide treatment in acute myeloid leukemia (AML) where the intensity of initial induction may be high (anthracycline and cytarabine-based), intermediate (venetoclax combinations), or low (single hypomethylating agent or targeting therapy). Fried’s Frailty Phenotype (FP) combines subjective (self-reported exhaustion, weight loss > 5%, activity level) and objective (4-meter walk speed and grip strength) measures to categorize patients into fit, pre-frail, and frail. In prior work, we demonstrated an association of FP with survival for newly diagnosed older adults with AML. Clinical Frailty Scale (CFS) is a purely subjective score that utilizes chart data to stratify the degree of fitness. The incorporation of objective measures into clinical practice is limited due to time constraints, we sought to determine if CFS could similarly identify frailty and risk-stratify older adults with AML. Methods: Eighty-three patients 60 years or older with a new diagnosis of AML were enrolled on an IRB approved study from September, 2018 to May, 2023 at the Hospital of the University of Pennsylvania. FP was performed prior to initiation of therapy. A CFS certified trainee blinded to FP scores retrospectively reviewed electronic medical records to assign a CFS score. CFS was collapsed into variations defined as CFS fit (1-3), pre-frail (4), and frail (5 or greater); CFS Collapse 1 fit (1-2), pre-frail (3-4), and frail (5 or greater), and CFS Collapse 2 fit (1-4) and mild to moderately frail (5-6). Variations were based on the scale’s descriptions and literature. Results: Median patient age was 71 (range 60-91) years. By European LeukemiaNet 2017, 64% of patients had adverse-risk AML. 39% of patients received IC, 52% received HMA/ven, 6% received HMA alone or targeted therapy, and 2% received supportive care. By FP, 18% were fit, 38% were pre-frail, and 45% were frail. FP was significantly associated with OS (p = 0.047): 2-year OS was 57%, 42%, and 21% in fit, pre-frail, and frail. By CFS, 43% were fit, 32% pre-frail, and 24% frail. CSF was not significantly associated with OS (p = 0.495); 2-year OS was 24%, 35%, and 19% for fit, pre-frail, and frail patients, respectively. CSF collapse 1 (p = 0.249) and 2 (p = 0.070) were not significant. Conclusions: FP identified more patients as frail and was associated with a doubling of early mortality and inferior 2-year OS. CFS identified more patients as fit and was not associated with 2-yr OS. The discrepancy emphasizes the importance of objective measurements to capture frailty and the difficulty in determining frailty based on chart reviews in an acutely ill population. Future work to streamline objective measurements in frailty assessments to increase utilization in clinics given its likely importance for accurate risk-stratification.

Relationship between Mitochondrial Oxphos Kinetics and Response to Induction Chemotherapy in Patients with Acute Myeloid Leukemia

Background: Acute myeloid leukemia (AML) is an aggressive hematologic malignancy carrying a poor prognosis. Relative to non-leukemic myeloid progenitors, AML cells present with elevations in mitochondrial metabolism driven by higher mitochondrial content. Despite having more mitochondria per cell, AML cells are inefficient at coupling respiration to ATP synthesis, indicative of intrinsic deficiencies in oxidative phosphorylation (OXPHOS) flux. The present study aimed to determine the relationship between mitochondrial OXPHOS kinetics and chemotherapy response in a clinical cohort of AML patients by comparing mitochondrial bioenergetic profiles between responders to induction chemotherapy with those who have persistent disease, and between adverse risk and intermediate risk AML. Methods: In this prospective study from January 2020 to February 2023, we collected bone marrow aspirate samples from patients with new diagnosis of AML on day 1 to evaluate the bioenergetic phenotype of the AML cells. We collected data on primary induction therapy, response to induction therapy, relapse, and other clinical features. We compared the bioenergetic phenotypes between the responders to primary induction chemotherapy and non-responders who had persistent disease post induction chemotherapy. We did the same comparison between patients with adverse risk and intermediate risk AML per European LeukemiaNet (ELN) 2022 risk stratification. Mitochondrial bioenergetic profiles were generated via high resolution respirometry using freshly isolated mononuclear cells from each patient's bone marrow aspirate. The Fisher exact test was used for categorical variables and the Wilcoxon Rank Sum for continuous variables. Results: In 18 AML patients included in the study, median age was 64 years (range 30-85 years), 67% (N=12) were male, 33% female, 61%(n=11) were Caucasian and 39%(n=7) were African Americans. Day 1 median blast count was 57% (range 20-92%). Initial induction therapy with cytarabine/daunorubicin (standard 7+3) with or without midostaurin (in patients with FLT3 mutations) was done in 12 (67%) patients and hypomethylating agent/venetoclax was used in 5 (28%) patients. One patient was managed with azacitidine only. Seven (39%) patients had persistent disease after induction and others responded to the initial induction. Relapsed disease after achieving remission with initial induction was seen in 8 (44%) patients. No patients had favorable risk cytogenetics/molecular findings, 10 had adverse risk AML and 9 had intermediate risk AML. TP53 mutation was observed in 4 patients, FLT3 mutation in 5 patients, IDH1 mutation in 4, and IDH2 mutation in 3 patients. The fraction of the respiratory network capable of performing OXPHOS (i.e., Fractional OXPHOS) was 0.426 in responders and 0.629 in non-responders (p=0.93). In responders, basal respiration in intact cells was non-significantly (p=0.54) lower ( JO2 9.838 pmol/s/million cells) compared to non-responders ( JO2 11.52 pmol/s/million cells). Adverse risk patients had lower fractional OXPHOS, and higher basal and maximal respiration rates as compared to intermediate risk AML patients (Table 1). Conclusion: While Fractional OXPHOS and basal respiration were lower in the patients who had remission after induction therapy, this difference was not statistically significant. We did not find a clinically significant correlation in the bioenergetic profile of AML cells; however, our study is limited by small sample size. Further research is warranted to investigate the role of OXPHOS kinetics in patients of AML that can translate into clinically meaningful outcomes.

FLT3 Testing and Clonal Evolution in Patients with Acute Myeloid Leukemia: A Retrospective Cohort Study in Taiwan

INTRODUCTION: Mutation of the FMS-like tyrosine kinase 3 ( FLT3) gene is one of the most common genetic alterations in acute myeloid leukemia (AML), while FLT3 internal tandem duplication (ITD) is a predictor of poor disease prognosis in patients. Timing of FLT3 mutation testing and the pattern of FLT3 clonal evolution are critical issues for ensuring that patients with FLT3 mutation-positive AML receive targeted therapy promptly, but data from real-world clinical practice are limited. AIM: This retrospective cohort study aimed to assess the turnaround time of FLT3 testing in two patient cohorts with non-M3 primary AML: newly diagnosed (ND) patients and those with relapsed or refractory disease (R/R). A further aim in the R/R cohort was to assess the pattern of FLT3 clonal evolution. METHODS: Eligible adult patients had evidence of new diagnosis of AML or R/R AML between 1 January 2009 and 31 December 2019 and had undergone at least one FLT3 test at National Taiwan University Hospital. Patients were followed up until either the end of the data period, loss to follow up (no records for 6 months), or death. We analyzed the time from the date of ordering FLT3 test to receipt of results (both cohorts) and the acquisition (negative at diagnosis, positive at R/R), loss (positive at diagnosis, negative at R/R), or maintenance (no change in status) of FLT3 mutation at R/R compared with status at diagnosis. We also explored the association between acquisition/loss/maintenance of FLT3 mutation at R/R and overall survival (OS) in the R/R cohort. RESULTS: From a total AML dataset of 1,789 patients, 659 and 223 were included in the ND and R/R cohorts, respectively ( Table 1). Demographics and clinical characteristics of the ND and R/R cohorts were similar. The most common type of AML was recurrent genetic abnormalities in both ND and R/R cohorts (50.7% and 67.7%, respectively); 45.8% and 48.0% of patients, respectively, had a normal karyotype; and NPM1 (21.1% and 16.6%, respectively), and IDH1/ IDH2 (18.5% and 15.2%, respectively) were the most common types of co-mutations detected. There was no difference in the turnaround time of FLT3 testing between the ND and R/R cohorts ( Table 1). Since 2020, FLT3 testing protocols have been further optimized to meet a 7-day turnaround time; additionally, almost all chemotherapy-fit patients with FLT3 mutation receive midostaurin in combination with 3+7 chemotherapy after reimbursement of midostaurin was implemented in Taiwan in February 2020. Of 164 patients with FLT3 tests at both diagnosis and R/R, most (75.6%, n=124) were FLT3 mutation-negative at diagnosis ( Table 1). At R/R, 27/124 (21.8%) acquired an FLT3 mutation and 12/40 (30.0%) patients lost their FLT3 mutation ( Table 1). Risk of mortality was increased in patients who acquired an FLT3 mutation (HR [95% CI] 1.59 [0.97, 2.62]), maintained their FLT3 mutation (1.52 [0.58, 2.56]), or lost their FLT3 mutation (1.22 [0.58, 2.56]), compared with those who were FLT3-mutation negative at both diagnosis and R/R ( Figure 1). CONCLUSIONS: This study provided information on the real-world landscape of FLT3 testing among patients with AML in Taiwan. The turnaround time of FLT3 testing in the current study was longer than the time reported in clinical trials, likely owing to different procedures in sampling arrangement and report delivery between real world and clinical trial settings. The distribution of FLT3 mutation and pattern of clonal evolution were largely consistent with previously published clinical studies. The higher prevalence of FLT3 mutation in the R/R cohort versus the ND cohort is in accordance with previous research showing that FLT3-ITD mutation is predictive of relapse. Patients with FLT3 mutation at R/R had a shorter OS, which indicates the importance of FLT3 testing at R/R diagnosis to optimize outcomes through targeted therapy.

Use of Geriatric Assessment and Genetic Profiling to Personalize Selection of Intensive Versus Low Intensity Chemotherapy in Older Adults with Acute Myeloid Leukemia (AML): Final Results of a Phase II Trial

Introduction: Geriatric assessment can predict the risk of toxicities of chemotherapy in older adults. Genetic risk categories are associated with survival following intensive chemotherapy in AML. Integrating geriatric assessment for patient profiling and genetic profiling of leukemic cells represents an innovative precision medicine approach to personalize therapy selection in older adults with AML. We report final results of a pragmatic phase II trial using such strategy, aiming to reduce early mortality (NCT03226418). Methods: Patients ≥60 years with a new diagnosis of AML underwent geriatric assessment prior to initiation of treatment. Geriatric assessment of physical function, cognitive function and comorbidity burden were used to determine fitness for intensive chemotherapy (Table 1). Additional assessment included Karnofsky Performance Scale (KPS), Patient Health Questionnaire-9 (PHQ-9), and Mini Nutritional Assessment-Short Form (MNA). Genetic profiling for therapy selection relied on karyotyping and followed the 2017 European LeukemiaNet criteria. While available mutation test results were incorporated to risk stratify, the study did not require waiting for the results prior to therapy initiation, given an anticipated turnaround time of 1-2 weeks for mutation test results. Therapy selection followed the algorithm in Figure 1. Patients with good or intermediate-risk AML received intensive chemotherapy such as 7+3 +/- gemtuzumab or midostaurin if determined to be fit. Patients with high-risk AML received low-intensity chemotherapy such as a hypomethylating agent with or without venetoclax or novel drugs (based on timing of FDA approval of these drugs), or CPX 351 if they were fit and met the FDA-approved indications. Patients with organ dysfunction (e.g. creatinine ≥2 mg/dl) and those requiring chemotherapy for other malignancy were eligible for low-intensity chemotherapy. Chemotherapy could be administered in community oncology settings. Patients were followed for quality of life assessments, as well as functional and oncologic outcomes. Results: Between July 2017-October 2022, 75 patients were consented; 2 patients were considered screen failure. Baseline characteristics of 73 eligible patients included a median age of 69 years (range 60-87 years), 49% female, 92% white, and a median KPS of 80 (range 60-100). As presented in Table 1, most had ≥3 comorbidities (55%), impaired physical function measured by Short Physical Performance Battery (70% had a score of 9 or less) and impaired cognition measured by Montreal Cognitive Assessment (64% had a score of 25 or less). Genetic risk categories included adverse (62%), intermediate (22%), and good-risk AML (16%). Patients had one or more of the following mutations: TET2 (26%), NPM1 (22%), RUNX1 (19%), ASXL1 (19%), TP53 (19%), DNMT3A (16%), IDH2 (15%), IDH1 (11%), FLT3 ITD (10%), FLT3 TKD (10%), biallelic CEBPA (4%), EZH2 (2%). Seven patients (10%) received intensive chemotherapy; CPX 351 (n=4) or 7+3 based regimen (n=3). Other patients received low-intensity chemotherapy: azacitidine or decitabine and venetoclax (n=43, 59%), decitabine or azacitidine alone (n=18, 24%) prior to approval of venetoclax, and other (n=5, 7%). The median time from diagnosis to therapy initiation was 6 days and from enrollment to therapy initiation was 1 day (range 0-13). Mortality at 30 days from diagnosis was 6.8% (95% confidence interval, CI 3.0-15.1%) and at 90 days was 21.9% (95% CI 14.0-32.7%). Mortality compared favorably to an unmatched historical cohort of patients ≥60 years treated at our center between 2011-2016, where 30-day mortality was 30% (95% CI 22-40%) and 90-day was 41% (95% CI 32-52%) (Future Oncol. 2019;15:1989-95). Conclusions: Our model to personalize AML therapy selection represents an innovative approach to precision medicine that incorporates both geriatric assessment for patient profiling and genetic profiling of leukemia cells. Geriatric assessment demonstrated high frequency of impairment in objective physical and cognitive function. Patients were able to start therapy within a median of 1 day following enrollment. Pragmatic aspects of the trial included broad eligibility criteria and co-management of patients with community oncologists. The results from our final analysis appear promising with lower rates of early mortality compared to unmatched historical controls.

Venetoclax Combined with “7+3” Induction Chemotherapy Induces High Rates of MRD-Negative Remission in Newly Diagnosed AML Patients Fit for Intensive Chemotherapy Irrespective of Age

Introduction: Approximately 70% of patients (pts) with acute myeloid leukemia (AML) treated with the “7+3” regimen achieve complete remission (CR), with 30-50% of those attaining measurable residual disease (MRD) negative state by multiparameter flow cytometry (MFC). However, despite initial responses, the majority of pts eventually relapse. Venetoclax (Ven) added to intensive chemotherapy (IC) facilitates apoptosis of leukemic stem cells (LSC), and may result in deeper, more durable remissions. Moreover, IC induces MCL-1 downregulation and may overcome Ven resistance. We present safety and efficacy results from a phase 1b study of escalating cumulative Ven doses combined with daunorubicin (Dauno)+cytarabine (AraC) followed by high-dose cytarabine (HiDAC) chemotherapy in pts with newly diagnosed AML (NCT05342584). Objectives: The primary objective of this study is to determine the optimal dose of Ven in combination with Dauno & AraC and HiDAC chemotherapy. Secondary objectives are response per 2022 ELN, survival (OS), event-free survival (EFS) and duration of response (DoR). A key exploratory objective is to assess rates of LSC eradication by means of MFC and single cell DNA (Tapestri, Mission Bio) and RNA sequencing (“high-resolution MRD assay”). Methods: Eligible pts must have a new diagnosis of AML, be 18-75 yrs of age and deemed fit for intensive chemotherapy. In a 3+3 design, Ven in escalating duration (400 mg D1-8 or -11 or -14, including 2-day ramp-up) is combined with AraC 100mg/m2 (D2-8) and Dauno 60mg/m2 (D2-4) in 2 separate age groups (<60 and ≥60yrs); Dauno 90mg/m2 was initially studied in pts < 60yrs, but since 04/2023 the dose is no longer explored. During consolidation, fixed dose Ven (200 mg x7days) is used in combination with age-adjusted HiDAC (1.5g/m2 in <60yrs and 1g/m2 in ≥60yrs, every 12hrs on days 1,3,5). In the expansion phase, additional pts in each age group will undergo 1:1 randomization between the starting and highest tolerated dose determined during dose escalation, for a total of 20 pts per dose cohort in both phases. Results: Twenty-seven AML pts enrolled and 25 completed the induction phase to date, 2 are actively treated. Median age was 59yrs, 44% were females and 67% ethnic or racial minorities. Fourteen (52%) pts had poor-risk genotypes by ELN 2022. Fourteen pts were treated with Ven x 8d, 11 in Dauno60 and 3 in Dauno90 cohorts, 7 pts with Ven x11d and 6 pts with Ven x14d. No DLTs were observed, and the toxicity profile was similar to historical experience with the “7+3” regimen. There were no induction mortality deaths. Twenty pts (20/25, 80%) achieved a composite complete remission (CRc) with single induction (19 CRs and 1 CRi), 10/13 in <60 and 10/12 in ≥60yr groups. Median time to ANC≥0.5K/uL and PLT≥50K/uL was 26 days and time to CR was 32 days. Of those in CRc, all except three pts < 60yrs were MFC-MRD negative (17/20, 85%). Among 8 patients with available MRD PCR testing, 6 achieved molecular MRD-negative and 2 low-level molecular MRD CRs. With a median 5.6-month follow-up time, median EFS or OS have not been reached, 25/27 (93%) patients are alive (10/12 ≥60yrs), 12 pts have completed the protocol, 5 continue on therapy and 5 underwent allogeneic transplantation. From those in CRc, 7 younger and 8 older pts (75%) remain in remission without evidence of hematologic or molecular relapse. Of 5 pts with complex karyotype plus TP53 mutated AML, 3 did not respond and 2 had an early treatment failure. Table 1 summarizes patient characteristics, toxicity and outcomes. Conclusions: Ven 400mg in combination with “7+3” induction chemotherapy is safe and highly effective in achieving MRD negative remissions in the vast majority of patients. Responses were low in TP53 mutated pts, suggesting no benefit of the addition of venetoclax to intensive chemotherapy, similar to what has been observed when venetoclax is added to standard dose hypomethylating agents in those pts, for whom non-cytotoxic approaches are being explored. The study is completing enrollment in the Dauno60 + Ven x14d cohorts and is entering the expansion phase in order to better explore the optimal Ven dose to combine with the “7+3” regimen. Updated results, as well as rates of LSC elimination post-induction will be presented at the meeting.

Older Adults with Acute Myeloid Leukemia (AML) Treated in a Pragmatic Trial: How Do Patients’ Function and Health-Related Quality of Life Change with Treatment?

Background: Over one-third of older adults with AML do not receive chemotherapy because of fear of toxicities and functional decline. This highlights the critical and urgent need to generate knowledge of functional changes following newer treatments. Methods: As a part of a pragmatic single-center phase II investigator-initiated trial (ClinicalTrials.gov ID: NCT03226418), we enrolled older adults (≥60 years) with a new diagnosis of AML. We repeated geriatric assessment (GA) and health-related quality of life (HRQOL) before and 3 months after chemotherapy initiation. GA included measures of physical function (e.g. short physical performance battery or SPPB), Montreal Cognitive Assessment (MoCA), Hematopoietic Cell Transplantation Comorbidity Index, Patient Health Questionnaire-9 (PHQ-9), Mini Nutritional Assessment-Short Form. Frailty was defined as impairment in 2 or more domains on geriatric assessment (excluding MoCA). HRQOL was measured using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C-30 (v 3.0). Established cutoffs were used to determine a clinically meaningful change in various measures from baseline to 3 months. Results: 59 eligible patients were enrolled and had median age of 69 years and median KPS of 80. Patients received treatment with predominantly low-intensity chemotherapy (hypomethylating agent +/-venetoclax or midostaurin); six patients received intensive chemotherapy. 56% of patients had ≥2 comorbid conditions, and 69% each had impaired MoCA scores and impaired objective physical function at baseline. Whereas 29% had an established diagnosis of depression or anxiety, 66% had abnormal PHQ-9 with a score of 5 or more. 61% had impaired nutritional screen. A total of 43 patients completed some or all of the optional follow-up assessments at 3 months. Cognitive function or MoCA scores improved (64.5%) or stabilized (9.6%) from baseline to 3 months after treatment (Figure 1). We also noted improvement (51.6%) or stabilization (22.6%) in objective physical function (Figure 2). PHQ-9 scores showed improvement or stabilization in about 90% of patients. Nutritional scores showed variable changes with 40% demonstrating improvement. On HRQOL assessment, global health status score, and role functioning moderately improved from baseline to three-month after enrollment. Longitudinal cognitive function over 3 months differed based on the presence of frailty and multimorbidity (≥2 comorbid conditions) at baseline. Improvement in MoCA scores was noted in 31.8% (95% CI 16.4-52.7%) and 50.0% (95% CI 23.7-76.3%) of patients with versus without baseline frailty. The risk of worsening of cognitive function was 31.5% (95% CI 15.4-54.0%) for patients with multimorbidity at baseline versus 16.7% (95% CI 4.7-44.8%) for those without. Conclusion: We demonstrated an overall improvement or stabilization of functional status and HRQOL in a high proportion of older adults with AML, despite high prevalence of functional impairments and significant comorbidity burden at baseline. These results should encourage oncologists to offer chemotherapy even to older adults with multiple comorbid conditions or poor functional status at the time of diagnosis of AML. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Venetoclax Plus Intensive Chemotherapy in AML and Advanced MDS: Assessment of Leukemia Stem Cell Eradication By High-Resolution MRD Assay

Background: For the past five decades the standard of care for fit patients with acute myeloid leukemia (AML) has been induction with the "7+3" regimen, using a combination of cytarabine (AraC) and anthracycline (daunorubicin, idarubicin) followed by consolidation high-dose AraC (HiDAC). With this approach, approximately 70% of younger (≤60 years of age) and 60% of older (>60 yrs) fit patients achieve a complete remission, with 30-50% of those patients attaining measurable residual disease (MRD) negative state by multiparameter flow cytometry (MFC). However, even patients with MRD-negative remissions relapse due to remaining chemotherapy-resistant pre-leukemic and leukemic stem cells (LSCs). Eradication of residual disease at the LSC level is therefore the ultimate goal to achieve durable remissions and cure. The combination of Venetoclax (Ven) with chemotherapy can have a synergistic effect; by reducing the apoptotic threshold, Ven can facilitate increased apoptosis induced by genotoxic agents, while at the same time chemotherapy can downregulate MCL-1 that drives Ven resistance. Ven in combination with hypomethylating agents has shown to not only eradicate AML blasts but also target and eliminate LSCs. Early phase trials combining Ven with intensive chemotherapy (IC) have shown encouraging safety and efficacy signals. However, the optimal dose and schedule of Ven that can best synergize with IC to eradicate LSCs remain unknown. Here we present a phase 1b study evaluating the safety and tolerability of Ven in combination with daunorubicin (dauno)/AraC) induction followed by HiDAC consolidation in patients with newly diagnosed AML or high-risk myelodysplastic syndrome (MDS). Objective: The primary objectives of this study are to evaluate the safety, tolerability, and to determine the maximum tolerated dose (MTD) of the combination of Ven plus dauno & AraC, as well as HiDAC IC. Secondary objectives are response per 2017 ELN and revised IWG criteria, survival, event-free survival and duration of response. A key exploratory objective is to comprehensively analyze LSC and assess rates of LSC eradication by means of MFC and single cell sequencing ("high-resolution MRD assay"). Design: This is a Phase 1b, open-label, dose-escalation study, evaluating Ven in combination with IC in previously untreated, adult patients with AML and high-risk MDS (NCT05342584). In Part 1, we are utilizing a 3+3 design to evaluate the safety and tolerability of different Ven doses in combination with IC. In Part 2, we will evaluate the safety and clinical activity in additional 12 patients at the dose determined in Part 1. To evaluate for LSC MRD, bone marrow aspirates obtained at the time of each disease evaluation will be analyzed by high-resolution MRD assays. Specifically, we will perform multicolor flow cytometry assays optimized for primary samples and able to distinguish, quantify, and sort pre-LSCs and LSCs. Furthermore, we will combine this assay with ultra-deep sequencing (1Million x) to detect very low levels of mutant cells, importantly within the LSC compartment. Eligible patients must have a new diagnosis of AML or high-risk MDS (blasts>10% AND R-IPSS>3.5%), be 18-75 yrs of age and deemed fit for intensive chemotherapy. During induction, escalating Ven doses (400 mg x8 -> 11 -> 14 days) will be combined with AraC 100mg/m2 and 2 doses of dauno (60 and 90mg/m2) in patients aged 60yrs or younger, whereas dauno 60 will be used for all patients older than 60yrs. During consolidation, the Ven dose will be escalated (200 -> 400mg) in a similar 3+3 design at a fixed 7-day duration in combination with age-adjusted high dose AraC regimen (1.5g/m2 in ≤60yrs and 1g/m2 in >60yrs, every 12hrs on days 1,3,5). Conclusion: This study will evaluate the optimal dosing of Venetoclax and daunorubicin as part of the Ven plus "7+3" induction regimen. It will also evaluate the optimal dose of Venetoclax in combination with HiDAC consolidation chemotherapy. This trial will utilize a novel highly-sensitive LSC MRD assay to test the efficacy of Venetoclax in eliminating LSCs when combined with conventional chemotherapy.

EE33 Evaluating the Economic Burden of Acute Myeloid Leukemia in Canada

Acute myeloid leukemia (AML) represents a significant burden for patients, their families and the healthcare system. This study estimated the total cost of illness associated with a new diagnosis of AML in Canada.

Time at home among older adults with acute myeloid leukemia based on treatment intensity: A SEER-Medicare analysis.

6586 Background: Older adults with acute myeloid leukemia (AML) have identified time at home (TAH) as a critical outcome when deciding on treatment. No study to date has fully explored TAH for older adults with AML. Methods: We identified a cohort of adults age ≥66 years with a new diagnosis of AML from the SEER-Medicare linked database from 2004-2016. Individuals were stratified into high-intensity chemotherapy [HIC] v. hypomethylating agent [HMA] v. other using claims. The primary outcome was TAH, quantified by subtracting the total number of person-days spent in hospitals and skilled nursing facilities from the number of person-days survived. Demographics, comorbidities, frailty, and transfusion dependence were considered covariates. Results: 7,946 adults were included. 2,824 (36%) received HIC, 2,542 (32%) HMA, and 2,580 (33%) other. Mean age was 75 years (HIC: 73; HMA: 78; other: 76). The cohort was predominantly White (88%, Black 5%; Asian 3%; Hispanic 1%) and male (57%). Median survival was 7 months (HIC: 9; HMA: 8). Median total TAH was 151 days (Mean 426, Range 0-1825). Adults receiving HIC spent less time at home and more time hospitalized than those receiving HMAs each month in the first year (Table). Differences in TAH between HIC and HMA cohorts were most pronounced in the first 3 months (1st: 49.5% v. 86.5%; 2nd: 68.2% v. 84.1%; 3rd: 77.3% v. 86.8%). Total TAH over 12 months was lower for those receiving HIC v. HMA (51.7% [187 days] v. 56.9% [205 days]). Transfusion dependence (≥ 1/month) was associated with decreased TAH at 1 month (OR 0.81, p<0.001) and 12 months (OR 0.90, p=0.04). Other covariates were not associated with TAH. Conclusions: Although intensive chemotherapy resulted in slightly longer survival, older adults treated with HMAs had more time at home. Treatment decision-making should incorporate patient preferences for prolonging survival v. increasing time at home. The effect of new treatments (eg, venetoclax) on time at home should be evaluated in future studies. [Table: see text]

Psychological mobile app for patients with acute myeloid leukemia (AML): A randomized clinical trial.

12018 Background: Patients with AML experience substantial decline in their quality of life (QOL) and mood during their hospitalization for intensive chemotherapy. Yet, few interventions have been developed to enhance patient-reported outcomes during treatment. Methods: We conducted a randomized trial of a psychological mobile app (DREAMLAND) for patients with a new diagnosis of AML receiving intensive chemotherapy at Massachusetts General Hospital and Dana-Farber Cancer Institute. Patients were randomly assigned to DREAMLAND or usual care. DREAMLAND was tailored to the AML trajectory and included four required modules focused on 1) supportive psychotherapy to help patients deal with the initial shock of diagnosis; 2) psychoeducation to manage illness expectations; 3) psychosocial skill-building to promote effective coping; and 4) self-care. The primary endpoint was feasibility defined as at least 60% of eligible patients enrolling, and 60% of those enrolled completing at least 60% of the required modules. We assessed patient QOL (Functional-Assessment-of-Cancer-Therapy-Leukemia), psychological distress (Hospital-Anxiety-and-Depression-Scale [HADS] and Patient-Health-Questionnaire-9 [PHQ-9]), symptom burden (Edmonton-Symptom-Assessment-Scale), and self-efficacy (Cancer Self-Efficacy Scale) at baseline and day +20 post chemotherapy. We used ANCOVA to assess the effect of DREAMLAND on outcomes. Results: We enrolled 66.7% (60/90) of eligible patients and 62.1% completed ≥ 75% of intervention modules. At day +20 after intensive chemotherapy, patients randomized to DREAMLAND reported improved QOL (132.06 vs. 110.72, P = 0.001), lower anxiety (3.54 vs. 5.64, P = 0.010) and depression (HADS: 4.76 vs. 6.29, P = 0.121; PHQ-9: 4.62 vs. 8.35, P < 0.001) symptoms, and improved symptom burden (24.89 vs. 40.60, P = 0.007) and self-efficacy (151.84 vs. 135.43, P = 0.004) compared to the usual care group. Conclusions: A psychological mobile app for patients newly diagnosed with AML is feasible to integrate during hospitalization for intensive chemotherapy and may improve QOL, mood, symptom burden, and self-efficacy. Clinical trial information: NCT03372291.

Improved outcomes among newly diagnosed patients with FMS-like tyrosine kinase 3 internal tandem duplication mutated acute myeloid leukemia treated with contemporary therapy: Revisiting the European LeukemiaNet adverse risk classification.

Mutations in fms-like tyrosine kinase 3 (FLT3) gene are common genomic alterations in acute myeloid leukemia (AML). FLT3 internal tandem duplication mutations (FLT3-ITD) have consistently been shown to be adversely prognostic, particularly those with high allelic ratio (AR). Current AML treatment strategies, including high dose cytarabine, purine analogs, FLT3 inhibitors (FLT3i), and with or without allogeneic stem cell transplant (SCT) have been shown to improve the outcomes in patients with FLT3 mutations. We analyzed a consecutive cohort of newly diagnosed patients with AML treated at a large academic medical center from January 2012 to January 2020. A total of 1576 patients with a new diagnosis of AML were reviewed. Among these, 1438 (91%) had molecular testing for FLT3 mutations and 21% (304/1438) had an FLT3 mutation, including 17% with an FLT3-ITD mutation. We show that FLT3-ITD high AR with NPM1 wild-type have significantly improved survival compared with other European LeukemiaNet (ELN) adverse risk disease. In multivariable cox proportional hazards model of patients receiving intensive or low-intensity induction regimens, FLT3 mutations did not have prognostic significance. The use of allogeneic SCT in CR1 for patients with FLT3 mutations appears to improve survival, particularly in those with ELN adverse risk disease. Overall, this data highlights the changing prognostic impact of FLT3 mutations in a contemporary era with appropriate use of induction therapy combined with targeted agents and allogenic SCT.

Effect of geriatric assessment (GA) and genetic profiling on overall survival (OS) of older adults with acute myeloid leukemia (AML).

7021 Background: GA can predict the risk of toxicities of chemotherapy in older adults. Genetic risk categories correlate with OS in AML. We previously reported a reduction in early mortality in a pre-planned interim analysis of a phase II trial with the use of GA and genetic profiling to personalize therapy selection (NCT03226418) (Blood 2019; 134(s1):120). Here, we present the results of a propensity score matched analysis demonstrating an improvement in OS over a historical control. Methods: Patients ≥60 years with a new diagnosis of AML underwent GA. Patients were considered fit for intensive chemotherapy if they had robust physical function [normal activities of daily living (ADL) and instrumental ADL, and short physical performance battery score of ≥10 out of 12], normal cognitive function (Montreal Cognitive Assessment score of ≥26 out of 30), and hematopoietic cell transplantation comorbidity index (HCT CI) of 0-2 (except for treatment related AML, where a score of 0-2 in addition to the prior history of malignancy was acceptable). Genetic profiling for therapy selection relied on karyotyping and followed the 2017 ELN criteria. Fit patients with good or intermediate-risk AML received intensive chemotherapy. Patients with high-risk AML received low-intensity chemotherapy, or CPX 351 if they were fit and met the FDA-approved indications. Pragmatic aspects of the trial included broad eligibility criteria (e.g. patients on treatment for other malignancy were enrolled) and co-management of patients with community oncologists. Mortality was compared with a historical control treated during the years 2004-2016 (after approval of HMA) and matched on gender, age, Karnofsky Performance Status (KPS), HCT CI and ELN risk category. Results: Treatment group (n = 27) vs. historical controls (n = 32) were matched in terms of age (median age, 70 vs. 68.5 years), ELN risk category (adverse risk 59% vs. 53%), HCT CI (median score of 2), KPS (median 80 vs. 85), and gender (male 44% vs. 50%). In the treatment group, 3 patients received intensive chemotherapy: CPX 351 (n = 2) or 7+3+ gemtuzumab (n = 1). Other patients received HMA alone (n = 16), decitabine and midostaurin (n = 3), or azacitidine and venetoclax after the approval of venetoclax (n = 5). Treatment in the historical control included intensive chemotherapy (n = 20) such as 7+3, or mostly HMA based low intensity chemotherapy (n = 12). OS was significantly higher in the treatment group over historical control with 1-year OS of 66% (95% CI 60-87%) vs. 16% (95% CI 7-35%). Conclusions: Our model to personalize AML therapy selection represents an innovative approach to precision medicine that incorporates both GA for patient profiling and genetic profiling of leukemia cells. Our results appear promising with superior OS (an absolute difference of 50% in 1-year OS) compared to a matched historical control. Clinical trial information: NCT03226418.

1150. Breakthrough Invasive Fungal Disease (IFD) in Patients with Acute Myeloid Leukemia (AML)

BackgroundDespite the use of antifungal prophylaxis, IFD remains a serious complication of AML causing extensive morbidity and mortality. This study seeks to clarify our experience with breakthrough infections in patients with AML.MethodsThis retrospective study included all adult patients undergoing induction chemotherapy for a new diagnosis of AML from June 2014 – Dec 2019 at the University of Michigan Hospital. Chart review determined co-morbidities, chemotherapy regimens, allogeneic hematopoietic cell transplant (HCT), antifungal prophylaxis, development of IFD, and outcomes. Patients were followed for 1 year from first induction chemotherapy. EORTC-MSGERC definitions for proven, probable, and possible IFD were used, as were MSGERC-ECMM definitions for breakthrough IFD.ResultsOf 251 patients, mean age was 61.8±14 years, 55% were men, and 73 (29%) underwent allogeneic HCT, 52 of whom developed GVHD. Thirty-one patients developed 33 IFD (12.3%): 4 proven, 12 probable, and 17 possible IFD. Four IFD occurred in patients with GVHD post-HCT; all were treated with high dose steroids and one received an anti-TNF agent. Of the 16 proven and probable IFD, 8 were breakthrough IFD. Mucormycosis occurred in 2 patients on voriconazole; fusariosis occurred in 3 patients taking fluconazole (2), or posaconazole (1). Aspergillosis occurred in 2 patients taking isavuconazole (1) or fluconazole (1), and pneumocystosis occurred in a patient receiving inhaled pentamidine. There were 8 non-breakthrough IFD, including 2 pneumocystosis, 4 aspergillosis, and 2 candidiasis. Risk for IFD increased with subsequent episodes of induction chemotherapy, p=.04.Six of 8 patients with breakthrough IFD and 5 of 8 without breakthrough IFD died within 12 weeks of IFD diagnosis. Excluding the 15 patients who had only possible IFD, 69% (11/16) patients with proven/probable IFD died compared with 35% (77/220) patients without IFD, p=.01.ConclusionPatients with AML remain at risk for fatal IFD despite the use of antifungal prophylaxis. Failure of prophylaxis in our patients who developed breakthrough IFD was associated with a shift towards less common fungi.Disclosures All Authors: No reported disclosures

Inferior Outcomes with a High LSC17 Score Can be Improved with Flag-IDA

Inferior Outcomes with a High LSC17 Score Can be Improved with Flag-IDA

Geographical Distance from Quaternary Treatment Center Does Not Impact Choice of Upfront Therapy, Clinical Trial Participation and Outcomes in Patients with Newly Diagnosed AML

Upfront therapy for newly diagnosed patients with acute myeloid leukemia (AML) includes intensive induction chemotherapy with curative intent, low dose chemotherapy, best supportive care, and clinical trials. The choice between these therapies is influenced by multiple factors including age, cytogenetic and molecular mutations, and performance status. In our single payer provincial health care system, induction chemotherapy and clinical trials are only offered at a small number of specialized quaternary care centers with geographically large catchment areas. As a result, some patients are required to travel long distances for their appointments, which may constitute a barrier to care, especially among elderly patients. We therefore asked whether distance from the quaternary center influences the choice of care for AML. We reviewed the records of patients ≥18 years of age diagnosed with AML from 2015-2017 and assessed at our quaternary care center in Toronto, Canada. We compared upfront therapy choice and survival between patients living close versus distant from the cancer center (empirically defined as <50 km versus >50km) and stratified by age. A total of 675 patients were assessed by our quaternary center for a new diagnosis of AML during the timeframe studied. Of those patients, 477 (71%) patients lived ≤50km, and 198 (29%) patients lived >50km from the quaternary center. The overall median distance from patient residence to the quaternary center was 33.2km (range: 1-1791km), and the median distance of patients in the >50km group was 93km (range: 50.2-1791km). Age, sex, baseline Eastern Cooperative Oncology Group Performance Status (ECOG), and cytogenetic risk were not significantly different between the two groups. There were no differences in the proportion of patients receiving induction chemotherapy or clinical trial as upfront therapy between patients living close versus distant from the quaternary center, even when stratified for age ≥70 years. There was no difference in overall survival between patients living ≤50km versus >50km from the quaternary center either overall, or when stratified by age. In conclusion, geographic distance from treatment center does not appear to impact choice of upfront therapy, access to clinical trials, or clinical outcomes in this study of newly diagnosed patients with AML treated in a single payer environment. Disclosures Gupta: Bristol MyersSquibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Honoraria, Research Funding; Pfizer: Consultancy; Sierra Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees. Maze:Novartis: Honoraria; Pfizer: Consultancy; Takeda: Research Funding. McNamara:Novartis: Honoraria. Schimmer:Takeda: Honoraria, Research Funding; Novartis: Honoraria; Jazz: Honoraria; Otsuka: Honoraria; Medivir AB: Research Funding; AbbVie Pharmaceuticals: Other: owns stock .

Integrating Geriatric Assessment and Genetic Profiling to Personalize Therapy Selection in Older Adults with Acute Myeloid Leukemia (AML)

Introduction: Geriatric assessment can predict the risk of toxicities of chemotherapy in older adults. Genetic risk categories correlate with survival following intensive chemotherapy in AML. Integrating geriatric assessment for patient profiling and genetic profiling of leukemic cells represents an innovative precision medicine approach to personalize therapy selection in older adults with AML. We report results of a pre-planned interim analysis of a pragmatic phase II trial using such strategy that has an overarching goal to reduce early mortality (NCT03226418). Methods: Patients ≥60 years with a new diagnosis of AML underwent geriatric assessment prior to initiation of treatment. Geriatric assessment of physical function, cognitive function and comorbidity burden were used to determine fitness for intensive chemotherapy (Table 1). Additional assessment included Karnofsky Performance Scale (KPS), Patient Health Questionnaire-9 (PHQ-9), and Mini Nutritional Assessment-Short Form (MNA). Genetic profiling for therapy selection relied on karyotyping and followed the 2017 European LeukemiaNet criteria. While available mutation test results were incorporated to risk stratify, the study did not require to wait for the results prior to therapy initiation given an anticipated turnaround time of 1-2 weeks for mutation test results. Therapy selection followed the algorithm demonstrated in Figure 1. Patients with good or intermediate-risk AML received intensive chemotherapy such as 7+3 +/- gemtuzumab or midostaurin if determined to be fit. Patients with high-risk AML received low-intensity chemotherapy such as a hypomethylating agent with or without novel drugs, or CPX 351 if they were fit and met the FDA-approved indications. Patients with organ dysfunction (e.g. creatinine ≥2 mg/dl) and those requiring chemotherapy for other malignancy received low-intensity chemotherapy. Chemotherapy at diagnosis or follow up could be administered in community oncology settings. Patients were followed for assessment of quality of life, functional and oncologic outcomes. Results: Between July 2017-June 2019, a total of 31 patients (including 1 MDS patient considered screen failure) were enrolled. The pre-planned interim analysis results are based on the first 27 AML patients. Baseline characteristics included a median age of 70 years (range 60-84 years), 56% female, 96% white, and a median KPS of 80% (range 60-100%). As presented in Table 1, over half of the patients had ≥3 comorbidities, impairment in objective physical function (short physical performance battery) and Montreal Cognitive Assessment. Additionally, 67% had poor nutritional status (MNA score of ≤11) and 26% had abnormal depression screen (PHQ-9 score of ≥10). Risk categories included adverse (64%), intermediate (16%), and good-risk AML (20%). Patients had one or more of the following mutations: FLT3 ITD (11%), NPM1 (22%), biallelic CEBPA (4%), IDH1 (15%), IDH2 (8%), RUNX1 (15%), ASXL1 (22%), and TP53 (19%). Three patients received intensive chemotherapy; CPX 351 (n=2) or 7+3+ gemtuzumab (n=1). Other patients received decitabine or azacitidine alone (n=16), azacitidine and venetoclax (n=5) or decitabine and midostaurin (n=3). The median time from diagnosis to therapy initiation was 7 days (0-20 days) whereas the median time from enrollment to therapy initiation was 2 days (range 0-9). Mortality at 30 days from diagnosis was 3.7% (95% confidence interval, CI 0.7-18.3%) and at 90 days was 29.6% (95% CI 15.9-48.5%). Mortality compared favorably to an unmatched historical cohort of patients ≥60 years treated at our center between 2011-2016, where 30-day mortality was 30% (95% CI 22-40%) and 90-day was 41% (95% CI 32-52%) (Future Oncol. 2019;15:1989-95). Conclusions: Our model to personalize AML therapy selection represents an innovative approach to precision medicine that incorporates both geriatric assessment for patient profiling and genetic profiling of leukemia cells. Geriatric assessment demonstrated high frequency of impairment in objective physical and cognitive function. Patients were able to start therapy within a median of 2 days following enrollment. Pragmatic aspects of the trial included broad eligibility criteria and co-management of patients with community oncologists. Our pre-planned interim analysis data appear promising with lower rates of early mortality compared to unmatched historical controls. Disclosures Bhatt: Pfizer: Consultancy; CSL Behring: Consultancy; Agios: Consultancy; Abbvie: Consultancy; Partner therapeutics: Consultancy; Incyte: Consultancy, Research Funding; Tolero Pharmaceuticals: Research Funding; National Marrow Donor Program: Consultancy. Al-Kadhimi:Celldex Biotech: Other: Stocks; Seattle Genetics: Other: Stocks. Armitage:Oncology Analytics: Consultancy; Partner Therapeutics: Consultancy; Samus Therapeutics: Consultancy; Ascentage: Consultancy; Tesaro bio: Membership on an entity's Board of Directors or advisory committees; Union Pacific: Consultancy. Holstein:GSK: Consultancy; Genentech: Membership on an entity's Board of Directors or advisory committees; Sorrento: Consultancy; Celgene: Consultancy; Takeda: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees. Gundabolu:Samus Therapeutics: Research Funding; Jazz pharmaceuticals: Consultancy; Pfizer: Consultancy; Novartis: Consultancy. OffLabel Disclosure: Single agent azacitidine and decitabine as well as decitabine in combination with midostaurin are not approved by the US FDA for acute myeloid leukemia.

Distance Does Not Matter: Excellent Survival Outcomes for Leukemia Patients in Rural Appalachia

Background: Rural communities may not have access to adequate health care, but the effect of geographic residence on patient outcomes and molecular characteristics of acute myeloid leukemia (AML) is poorly understood. Several studies have investigated the effect of various demographics (such as race, gender, zip code) and environmental exposures on the development and outcome of AML. Evidence is lacking to suggest a link between genetic abnormalities and residence. Methods: A single center, retrospective chart review was conducted on patients with AML diagnosed between 9/2015 and 8/2018. Consecutive patients with a new diagnosis of AML and a clinical next generation sequencing panel (Illumina TruSight Myeloid 54 gene panel) performed during their initial leukemia workup were included. Patients were excluded if they had APML or CML in blast crisis. Data collected included demographic information (including zip code), smoking history, BMI, cytogenetic data, treatment regimen, and overall survival. Patients were grouped into urban and rural subsets based on their county of residency as described in the National Center for Health Statistics 2013 Urban-Rural Classification Scheme for Counties. Zip codes were used to extrapolate socioeconomic data including education and income level. Cytogenetic data was used to risk stratify patients per ELN criteria. Mutational profile, cytogenetics and overall survival (OS) were compared between the groups. Mutations analyzed were limited to ASXL1, DNMT3A, FLT3, IDH1, IDH2, NPM1, NRAS, TET2, and TP53, as these are often used in medical decision making. Multivariate logistic regression was conducted to evaluate differences between the groups. Time to event data were analyzed using log-rank tests, Kaplan-Meier method, and Cox proportional hazard regression model. Results: 113 patients were included in this study. Median age of the entire cohort was 66.3 years old. 59% (n = 67) were male. 24% (n = 27) of patients were from a rural area; 76% (n = 86) were from an urban area. There was no difference in median age, race, prior MDS or MPN, number of patients who underwent chemotherapy or number of patients who underwent allogeneic stem cell transplant (ASCT) as demonstrated in Table 1. Patients from both cohorts also had similar risk cytogenetics (urban cohort: favorable: n = 5, 5.8%; intermediate: n = 35; 40.7%; adverse: n=46; 53.5%; rural cohort: favorable: n = 3, 11.1%; intermediate: n = 14; 51.9%; adverse: n = 10, 37%; p = 0.282). In the rural cohort, 15% of patients reported income below the poverty level; in the urban cohort, 10.2% reported income below the poverty level (p < 0.0001). Fewer patients in the rural cohort were high school graduates as compared to the urban cohort (82.7% versus 87.8%, p < 0.0001). Rural patients traveled an average of 145 miles for treatment; urban patients traveled 57 miles (p < 0.0001). Mutation frequency is described in Table 2. ASXL1 mutation was more frequent in the urban cohort as compared to the rural cohort (p = 0.032). There was no difference in frequency of other mutations between the cohorts. The 2 year survival rate was 46% (n = 52) for the cohort; 2 year survival rate for the rural cohort was 70% (n = 19) and for the urban cohort was 38% (n = 33) (p = 0.011; Figure 1). 53 patients (urban: n =39, 66.1%; rural: n = 14, 77.8%; p = 0.35) underwent induction chemotherapy. Rural patients who underwent induction chemotherapy had an improved OS as compared to urban patients who underwent induction chemotherapy (p = 0.005). Conclusion: In this single center retrospective study, our data demonstrates: 1. Urban patients had an increased frequency of ASXL1 mutations; 2. Rural patients were more likely to live below the poverty level and not graduate high school; 3. Rural patients traveled a greater distance for treatment; 4. OS was improved in rural patients in this limited cohort. Our rural patients may have improved OS due to our close co-management with rural centers. These studies suggest that the biology of the AML is not worse in the rural cohort and intensive efforts at access, remote monitoring, and communication with local physicians may result in outcomes similar to urban patients. Further studies will be investigating improving access to leukemia and transplant care for patients with AML. Disclosures Balkrishnan: Merck and Company: Consultancy. Keng:Agios: Membership on an entity's Board of Directors or advisory committees.

Factors That Dictate Mental Coping Strategies Used By Patients with Acute Myeloid Leukemia

Introduction: How patients cope with a new diagnosis of a serious/life threatening disease has been studied in a variety of settings and diseases, but not in acute myeloid leukemia (AML). In AML patients are confronted with a unique situation of a life-threatening diagnosis and the prospect of intensive prolonged treatments ahead of them. The aim of the current study is to assess different modes of coping with the diagnosis of AML, and whether these strategies remain stable over time. Methods: Adult patients with a new diagnosis of AML who were candidates for intensive chemotherapy and agreed to participate in this study were enrolled. The second author (Dr. Dorfman), a trained psychiatrist, and the chief of the Psycho-Oncology service in our institute, interviewed the patients at diagnosis and 3 months later. In these sessions the patients completed the Mental Adjustment to Cancer (MAC) questionnaire. The Hebrew version of this instrument was previously validated and consists of 40 items that assess the ability to cope with cancer and provides information on four major coping styles: fighting spirit, hopelessness/helplessness, anxious preoccupation and fatalistic acceptance. For each scale we calculated the standard (Z) score. The internal reliability measure (Cronbach's alpha) was above 0.7 for all scales. The sociodemographic interview gathered information on age, education, marital status, living arrangements, country of birth, religion and financial status. Additional medical information was obtained from the electronic medical record of each patient. We compared continuous variables using paired T-test and χ2 to compare categorical variables. We used a multivariate linear regression model to predict which of the baseline characteristics is associated with the coping strategy score. Results: We enrolled 18 patients with a recent diagnosis of AML. The median age was 55 years, and 12 (67%) were males. At time of diagnosis women, single patients (non-married or divorced), and patients with the lowest or highest income levels were significantly more anxious. Those who experienced a major life event within the previous year expressed lowers levels of hopelessness and a lesser degree of a fatalistic mode of coping. On the other hand, male patients, as well as unemployed or patients with low income, tended to express a higher degree of fatalistic feelings. Female patients were less likely to have high levels of fighting spirits. The mode of coping did not remain constant over time, and scores in all 4 scales changed over time. In fact, MAC scores in our cohort at 3 months correlated with baseline scores only in the fatalistic scale ( rp = 0.67, p = 0.006). Conclusion: In patients with newly diagnosed AML facing intensive chemotherapy, socioeconomics factors and life experience dictate, at least in-part, the coping strategy. However, 3 months after starting treatment, these factors become less influential. It is possible that at this stage, other factors, such as response to treatment, residual physical and mental resources and long-term prognosis become more important. Disclosures Wolach: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaker; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaker.

PF280 INTENSIVE TREATMENT OF ELDERLY AML PATIENTS IS SAFE AND FEASIBLE, PRINCESS MARGARET CANCER CENTRE EXPERIENCE

Background:Acute myeloid leukemia (AML) is a clinically and biologically heterogeneous disease. The incidence of AML increases with age, with the median age at diagnosis currently 67 years. The outcome in older patients is worse than for younger patients, which relates to patient, disease characteristics and possibly changes in drug dosing. Treatment represents a challenge as there is variability in which of these patients will be offered curative intent therapy.Aims:To describe the clinical outcomes in older adults with acute myeloid leukemia treated with induction chemotherapy.Methods:A retrospective review was performed on all patients with a new diagnosis of AML defined by ≥20% blasts in peripheral blood or bone marrow (acute promyelocytic leukemia and myeloid sarcoma excluded), treated intensively at Princess Margaret Cancer Centre between February 2015 and August 2017. Statistical analysis with Kaplan‐Meier product‐limit method, Log‐rank test and Cox regression model were performed using version 9.4 of the SAS system for Windows (2002–2012 SAS Institute, Inc., Cary, NC).Results:We identified 283 patients with a new diagnosis of AML for whom induction chemotherapy was used as the frontline approach. Of these, 136 (48%) were ≥60 years (range 60–82). Demographic and clinical data of both age groups were well balanced. The median age at presentation for the younger cohort was 50 yrs (range 18–59) while for the older group was 68 yrs (range 60–82). Poor risk cytogenetics by MRC classification was more frequently seen in the younger population compared to the older group (27% vs 17%, P = 0.030). Type of induction chemotherapy was evenly distributed between the two groups. In total, 216 patients had a beneficial response (CR/CRi/morphologic leukemia free state) with no differences between the younger and older age groups (76% vs 77%, P = 0.73). There was no significant difference in early death between young (3%) and older population (5%) (P = 0.339).In the Univariate Cox regression model comparing the two groups, MRC Cytogenetics (P < 0.0001), type of induction chemotherapy (P = 0.0079), post induction response (P < 0.0001), white blood cell count (P < 0.0001), lactate dehydrogenase (P = 0.0015) and creatinine (P = 0.03) were predictive of a shorter survival. Neither the type of diagnosis or ECOG retained prognostic value. In the multivariate analysis only post induction response remained statistically significant for length of survival (P < 0.0001).With a median follow‐up of 13 months, older patients had a shorter OS (21.0 months) vs 31.6 months in the younger group (P = 0.0121), Figure 1. The older population was subsequently subclassified into 2 different age groups, 60–69 yrs, 70–79 yrs (1 patient ≥ 80 was identified and excluded from analysis) to further investigate the effect of increasing age on outcomes. Survival for the 60–69 yrs and 70–79 yrs was 22.0 and 17.2 months respectively (P = 0.473) Figure 2 Summary/Conclusion:This study shows that those older patients undergoing intensive chemotherapy have similar response rates and treatment related mortality compared to their younger colleagues. Furthermore, patients in the 70–79 group had similar median OS compared to their younger counterparts (60–69 yrs). Despite a greater proportion of younger patients having poorer risk disease, the older group had a worse OS suggesting that other disease and patient related factors are important. Transplant‐Molecular data using a 54 myeloid gene panel will also be presented at EHA.image