Initial Acute Myeloid Leukemia Research Articles

Healthcare Resource Utilization and Costs Among Newly Diagnosed and Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients: A Retrospective Cohort Study Using Contemporary US Claims

Introduction: Prognosis for acute myeloid leukemia (AML) patients is generally poor, with rapid progression and high probability of relapse. AML has previously been associated with high healthcare resource utilization (HRU). Changes in the AML treatment landscape may have impacts on the economic burden of AML: since 2017, seven new systemic therapies have been approved for various AML patient populations, including those unfit for intensive therapy. The frequency of hematopoietic stem cell transplantation (HSCT) has also increased over this period. This retrospective cohort study aims to characterize first-line (1L) and second-line (2L) healthcare resource utilization (HRU) and costs in newly diagnosed (ND) and relapsed/refractory (R/R) AML patients, in the context of newly available AML treatments from 2017-2022. Methods: A large US administrative claims database (Optum) was used to identify ND AML patients between January 1, 2016, and August 31, 2022. The “ND index date” was defined as the first date a non-R/R AML diagnosis code was observed. To confirm that the initial AML diagnosis represented a true case of AML, ≥2 subsequent AML diagnoses within 60 days post-index were required. A washout period of 12 months was used to confirm no previous AML diagnosis. ND patients were required to have continuous enrollment from 1 year prior to the index until at least 30 days after the index date or death, whichever was earlier. A subgroup of R/R patients was then identified: all ND cohort members who 1) had an R/R AML diagnosis code, 2) had continuous enrollment between ND and at least 30 days after the R/R index date, and 3) did not receive 1L HSCT after the ND index date were eligible for inclusion. In this subgroup, the “R/R index date” was defined as the first date an R/R AML diagnosis code was observed. Patient per-patient-per-month (PPPM) HRU and costs were followed through the earliest of HSCT, clinical trial enrollment, death, loss of enrollment, end of data availability (September 30, 2022),or R/R diagnosis (for ND patients only). All results were reported descriptively by line of therapy and treatment received (HSCT vs. non-HSCT). Subgroup analyses were performed by age category. Results: We identified 3,145 ND and 644 R/R AML patients who received treatment over the study period. 3.4% of all treated ND patients received HSCT in 1L (n=107), while 19% of all treated R/R patients received HSCT in 2L (n=122). HSCT patients were younger and healthier than non-HSCT patients, reflecting selection into HSCT treatment by underlying patient characteristics (for ND patients, mean age at diagnosis 71.4 vs. 61.1; Mean Charlson Comorbidity Index (CCI) score 2.8 vs. 2.0; unfit for intensive chemotherapy 69% vs. 36%, Table 1). Patients receiving HSCT in 1L and 2L appeared to have more outpatient encounters (ND: mean 7.4 vs. 5.6; RR: mean 7.5 vs. 6.1, PPPM) than those not receiving HSCT. Number of inpatient days appeared somewhat higher among transplant recipients in 1L, but were similar to non-transplant recipients in 2L ( Table 2). While baseline pre-AML costs increased with age in 1L ($4,478 among patients 75 or older, $3,508 among patients younger than 65, PPPM), 1L follow-up costs were highest in the youngest cohort and lowest in the oldest cohort ($74,083 vs. $40,547, PPPM). Treatment-associated PPPM costs (medical + pharmacy) appeared higher in 1L vs. 2L ($54,457 vs. $48,595). When stratified by transplant status, total PPPM costs for patients receiving HSCT in 1L were higher than for those not receiving HSCT ($74,538 vs. $53,751), driven primarily by higher medical costs ($70,757 vs. $50,283). The same pattern was observed in 2L transplant vs. non-transplant patients ($56,380 vs. $46,979 total costs, $51,712 vs. $41,986 medical costs). Conclusions: The economic burden of AML for both ND and R/R patients in the context of newly available therapies remains substantial. Total costs were comparable but slightly higher for 1L therapy as compared to 2L, and significantly higher among patients receiving HSCT compared to those not receiving HSCT in both 1L and 2L. Decreasing economic burden with age was driven by lower medical costs associated with higher rates of supportive/palliative care, suggesting a lack of available active treatment options among older AML patients.

Real-World Treatment Patterns and Overall Survival Among Newly Diagnosed and Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients: A Retrospective Cohort Study Using Claims Data

Introduction: Acute myeloid leukemia (AML) is a malignant disorder of the bone marrow, characterized by abnormal clonal proliferation and differentiation arrest of myeloid progenitor cells. Prognosis is generally poor and worsens with age. While curative therapies are available, they are often unavailable to older patients and those with significant comorbidities due to high morbidity and mortality associated with intensive therapy. Since 2017, seven new systemic therapies have been approved for various AML patient populations, including those unfit for intensive therapy. This study aims to characterize first-line (1L) and second-line (2L) treatment patterns and outcomes in newly diagnosed (ND) and relapsed/refractory (R/R) AML patients, in the context of these newly available therapies. Methods: A large US administrative claims database (Optum) was used to identify ND AML patients between January 1, 2016, and August 31, 2022. The “ND index date” was defined as the first date a non-R/R AML diagnosis code was observed. To confirm that the initial AML diagnosis represented a true case of AML, ≥2 subsequent AML diagnoses within 60 days post-index were required. A washout period of 12 months was used to confirm no previous AML diagnosis. ND patients were required to have continuous enrollment from 1 year prior to the index until ≥30 days after the index date or death, whichever was earlier. A subgroup of R/R patients was then identified: all ND cohort members who 1) had an R/R AML diagnosis code, 2) had continuous enrollment between ND index date and ≥30 days after the RR index date, and 3) did not receive 1L hematopoietic stem cell transplant (HSCT) after the ND index date were eligible for inclusion. In this subgroup, the “RR index date” was defined as the first date an R/R AML diagnosis code was observed. Demographic characteristics, clinical characteristics, and treatment patterns over time were reported descriptively. Treatment regimens over time were described using the following classification: HSCT, intensive chemotherapy without targeted agents, intensive chemotherapy with targeted agents, hypomethylating agent (HMA) therapy only, other targeted therapy, Venetoclax-based therapy, unspecified/other treatment, no treatment/supportive care only. Overall survival (OS) was described using the Kaplan-Meier estimator. All analyses were stratified by line of therapy and transplant status. Results: We identified 5,135 ND AML patients and 934 R/R AML patients (ND cohort: mean age at initial AML diagnosis 73.5 years, mean follow-up time 6.1 months). ND patients receiving transplant in 1L tended to be younger and had fewer comorbidities than those not receiving transplant ( Table 1). Over the entire study period, 61% of ND patients and 69% of R/R patients received some treatment for AML; older patients were more likely to receive supportive care only. In 1L, Venetoclax-based and intensive chemotherapy without targeted agents were the most common treatment regimens (21% and 17% of all ND patients). In 2L, Venetoclax-based and HMA-only therapies were most common (17% and 16% of all R/R patients). Increases in the use of novel therapies (Venetoclax, intensive chemotherapy with targeted agents, or other targeted therapies) were observed in both 1L and 2L over the study period ( Figure 1). 1-year OS among ND patients was 32% in non-transplant recipients, and 84% in transplant recipients; among R/R patients, 1-year OS from RR index date was 21% in non-transplant recipients and 81% in transplant recipients. Conclusions: The findings from the present study indicate substantial disease burden and ongoing unmet need among ND and R/R AML patients in the USA. While treatment patterns for AML have changed significantly following the advent of novel therapies (with 41% of 1L patients and 31% of 2L patients being treated with novel therapies in 2022), OS remained low. Notably, around 1/3 of patients with RR AML did not receive active treatment; these patients tended to be older and were more frail. Increasing off-label use of Venetoclax in 2L further underscores high unmet need for patients who require more effective treatment options.

Hematopoietic Stem and Progenitor Cells Acquire an Inflammatory Memory of the Acute Myeloid Leukemia Niche

Recent studies suggest that acute myeloid leukemia (AML) generates inflammation in the bone marrow (BM) niche to an extent that compromises the function of healthy hematopoietic stem and progenitor cells (HSPC) and impacts patient prognosis. AML xenograft studies have identified several pro-inflammatory mediators (IL-6, IL-1b) that are secreted into the BM niche by leukemic blasts. Prior work by our laboratory also showed contributions involving other AML-secreted factors, in regulating HSPCs in the leukemic niche. HSPC are cellular components of the innate immune system, but the full extent of their inflammatory adaptation by AML is unknown. To overcome some of the experimental constraints inherent in the xenograft approach, we first established non-conditioned congenic grafts of C1498 murine AML cells in C57B/6 recipients. Assessment of the BM revealed that, even at low AML burden, these animals contained a range of elevated pro-inflammatory factors. Single cell RNA-Seq studies of healthy HSPCs, obtained concurrently at sacrifice confirmed an inflammatory transcriptional signature in HSC and MPP populations, with GSEA enrichment for interferon-alpha and -gamma signaling pathways. These observations led us to hypothesize that AML-experienced (inflammation-primed) healthy HSPCs may acquire a durable long-term inflammatory memory that shapes their response to subsequent stimulation during relapse or infection. To test this hypothesis, we adoptively transferred FACS-sorted healthy AML-experienced HSPCs from C1498-engrafted mice (HSPC AML) into secondary recipients. HSPCs transplanted from PBS-injected recipients (HSPC PBS) serve as controls. To assess whether HSPC AML would respond to immune challenge more aggressively compared to HSPC PBS, we exposed these animals with a single-injection of lipopolysaccharide (LPS), followed by tissue harvest and analysis after 24 hours. Bulk RNA-Seq analysis of HSPC AML from the LPS-challenged recipients showed amplified GSEA signatures for tumor necrosis factor- and NF-kB signaling pathways compared to HSPC PBS. In addition, LPS-challenged HSPC AML showed amplified expression by several krüppel-like factors (KLF) genes. Analysis for transposase-accessible chromatin loci (ATAC-Seq), concurrently obtained from LPS-challenged HSPC AML echoed the enrichment of KLF motifs as well. Collectively, the C1498 model suggests that initial AML exposure programs HSPC AML for an amplified inflammatory and differentiation program. To further ascertain disease relevance and reproducibility we turned to a doxycycline-inducible (i)MLL-AF9 AML model. Given the low leukemic burden in the BM of C1498-grafted animals, we wanted to test the hypothesis that secreted factors accounted, at least in part, for the inflammatory memory. Indeed, injection of AML secreted factors from iMLL-AF9 models revealed a strong inflammatory signature in bulk RNA-Seq studies. To determine if innate immune priming in HSPC can be directly mediated by AML crosstalk, we exposed ex vivo-expanded HSPCs to purified secreted factors (SF AML) from (i)MLL-AF9 AML blasts, followed by a secondary inflammatory challenge with LPS seven days later. Gene expression analysis of SF AML-experienced LPS-challenged HSPCs confirmed myeloid-skewed progenitor differentiation and increased expression of inflammatory targets. Together, our data show for the first time that phenotypically normal, AML-experienced HSPCs carry a durable inflammatory legacy whereby primary exposure to AML secreted factors alters their response to secondary stimuli. Our experiments phenocopy observations of trained immunity in other experimental systems, and suggest the acquisition of an innate immune memory in the AML niche. Immune priming may impact the role of these HSPC in the context of inflammation associated with aging, or clones with predisposing molecular lesions such as TET2 or DNMT3A.

Low Socioeconomic Status Confers Poorer Real-World Overall Survival for Patients with Acute Myeloid Leukemia Treated in the Modern Era

Introduction: There has been considerable growth in the treatment armamentarium of acute myeloid leukemia (AML) in the last decade. However, there is a lack of recent real-world evidence examining trends in survival amidst this rapidly changing treatment landscape. Further, prior literature has demonstrated significant heterogeneity in outcomes across different demographic groups, with scant data to understand how newer therapies have impacted survival outcomes across demographic groups in a real-world setting. The objective of this study is to describe recent trends in overall survival (rwOS) among patients with AML and to examine associations between race, ethnicity, and socioeconomic status (SES) with rwOS over time. Methods: We conducted a retrospective cohort study with data from the nationwide Flatiron health (FH) electronic health record-derived de-identified database, which is comprised of predominantly community oncology-based sites. We included patients with ≥2 visits in the FH network with a confirmed diagnosis of AML between Jan 1, 2014 and Dec 31, 2022, with potential follow-up through May 31, 2023. Our exposures included year of diagnosis in 3-year periods (2014-2016, 2017-2019, 2020-2022), race, ethnicity, and area-level SES, as measured using the Yost Index at census block group level. Patient characteristics and treatment patterns were described overall and by time periods of AML diagnosis. The Kaplan-Meier method was used to estimate median rwOS and 95% confidence intervals (CIs) from the time of initial AML diagnosis; overall and stratified by time period of AML diagnosis. Cox proportional hazards models were used to estimate unadjusted and minimally-adjusted (for age and sex) hazard ratios (HR) and 95% CIs for associations between race, ethnicity, and SES (modeled separately) with rwOS overall and by year of AML diagnosis.. Results: A total of 10,062 patients were included in the analysis. The median (IQR) age at diagnosis was 70 years (58, 78) and 57% of patients were male. Three-fourths of the study population was White, and 70% of the cohort received care at the community oncology clinic. We identified more patients ≥75 years at diagnosis in 2020-2022 versus 2014-2016 (38% vs 31%) and an overall decrease in patients who underwent hematopoietic stem cell transplant (15% vs 21%). Although the overall proportion of patients receiving any first-line treatment was similar across time periods, fewer patients received induction chemotherapy-based regimens (29%) compared to less intensive therapies (e.g., venetoclax + hypomethylating agent; 34%) in later years. There were 6,132 deaths and an overall median rwOS was 14.2 months (95% CI 13.7-14.7). Age and sex-adjusted Cox models indicated no evidence of decreased risk of death for diagnoses in 2020-2022 (HR 0.98, 95% CI 0.92-1.05) or 2017-2019 (HR 0.95, 95% CI 0.90, 1.02) compared to diagnoses in 2014-2016. Adjusted Cox models showed no statistically significant associations between race or ethnicity with survival overall and across strata of AML diagnosis time periods. Consistent associations between the lowest SES and increased risk of overall mortality among patients with AML were observed across all time periods. Patients residing in areas in the lowest quintile of SES had increased risks of death across all three time periods (2014-2016: HR 1.18, 95% CI 1.00-1.38; 2017-2019: HR 1.28, 95% CI 1.09-1.50; 2020-2022: HR 1.21, 95% CI 1.02-1.43). Conclusion: Results of this real-world study indicate that persons with AML who are in the lowest SES group are associated with increased mortality risk, and this association persists across recent time periods. Race and ethnicity were not associated with survival in this study, although sample size was limited for some groups. Despite introduction of new therapeutic options and an increased utilization of less intensive therapies, we did not observe an increase in the overall proportion of patients with AML receiving first-line treatment. Additionally, we observed no improvement in survival outcomes across these time periods in a predominantly community-based setting. Our study adds to the growing evidence on the complex health inequities in AML and supports the persistent need for tolerable and accessible therapy to improve OS in AML. Future strategies and policies are urgently needed to offset the adverse effects of low SES to further improve outcomes for all patients with AML.

Toward a Measurable Residual Disease-Based Algorithm for Selection of Allogeneic Hematopoietic Stem Cell Transplant in Acute Myeloid Leukemia

Background: The diagnosis and management of acute myeloid leukemia (AML) have transformed in recent years with an improved understanding of leukemogenesis and improved methods of measurable residual disease (MRD) detection. Current treatment algorithms include consideration of allogeneic hematopoietic stem cell transplant (HCT) for intermediate and adverse-risk AML. MRD negativity is widely accepted as a predictive and prognostic marker for disease-free survival and overall survival. However, the clinical use of MRD status in consolidative HCT planning remains unclear. Methods: Two hundred thirty-three consecutive patients achieving complete remission (CR) as defined in ELN 2022 after receiving therapy at Massey Cancer Center were analyzed. MRD status was determined either by multiparameter flow cytometry, PCR-based sequencing, and/or next-generation sequencing. Patients were analyzed via retrospective chart review to obtain baseline characteristics, molecular and cytogenetic profiles, and survival data. Median overall survival (mOS) was calculated and compared using the Kaplan-Meier method. Continuous variables were compared using one-way ANOVA. Categorical variables were analyzed using Fisher's exact test. Results: In total,109 patients achieved MRD-negative CR and 124 patients achieved an MRD-positive CR. Of the MRD-negative patients, 42 went received HCT (39%). In the MRD-positive cohort, 44 underwent HCT (35%). Among the MRD negative group, those receiving HCT tended to be younger (52.1 y. [range: 24.8-71.7] vs 61. 8 y. (range: 27.1-82.9) p = 0.026) with fewer co-morbidities (Charlson comorbidity index [CCI] score: 3 [range: 2-9] vs 4 (range: 0-14), p = 0.322). We observed a similar trend in those who had MRD positivity at best response or at the time of transplant (age 55 y. [range: 24.5-72.2] vs 62 y. [range: 25.1-88], p = 0.142; CCI 4 [range: 2-7] vs 5 (range 2-11], p = 0.014). In the MRD-negative/no HCT group, 49.3% had ELN favorable-risk disease at initial AML diagnosis, 28.4% had intermediate risk, and 22.4% had adverse risk. In the MRD-negative/HCT group, 31% were favorable risk, 33.3% intermediate risk, and 35.7% were adverse risk. In the MRD-positive/HCT group, 46.3% favorable risk, 23.8% intermediate risk, and 29.5% were adverse risk. There were no significant differences in ELN risk between any group. MRD-positive patients who underwent HCT had a mOS of 25.7 m. vs 20.7 m. for no HCT (HR=0.68 [95% CI, 0.41-1.11], p = 0.125). The median OS was not reached for MRD-negative patients, regardless of receipt of HCT (HR=0.61 [95% CI, 0.30-1.23], p = 0.168). Patients undergoing HCT in MRD-negative CR had improved OS compared to those undergoing HCT with persistent MRD positivity (p = 0.006). Discussion: MRD positivity is a known predictor of relapse and decreased survival despite HCT. However, the use of MRD as a decision point predicting which patients will benefit from transplant a priori needs to be better understood. Our data suggest that MRD negativity has a more significant impact on overall prognosis than HCT status.Likewise, the negative impact of MRD positivity was not significantly abrogated by subsequent HCT. This highlights the need for refinement in HCT selection beyond ELN 2022 intermediate/adverse-risk patients, and new validated algorithms incorporating MRD status are warranted.

Real-World Treatment Patterns Among Patients with Newly-Diagnosed (ND)-Acute Myeloid Leukemia (AML) in the United States (US)

Introduction: Clinical trials are essential to establish the efficacy and safety of medical products; however, clinical trials may not always be representative of or generalizable to the intended patient population. Notably, patients with comorbidities, older adults, and patients from racial and ethnic groups are often under-represented in clinical trials for acute myeloid leukemia (AML) (Bierenbaum et al, Leuk Res, 2012). Real-world data (RWD) can provide insight into the utilization, effectiveness, and safety of treatment regimens in routine clinical practice and has demonstrated usefulness in understanding the current treatment landscape. The objective of this study was to describe patient characteristics and treatment patterns in the first-line setting among a real-world cohort of adult patients with ND-AML in the US. Methods: This retrospective observational study used the COTA real-world database, a de-identified source of longitudinal electronic health record (EHR) data pertaining to the diagnosis, clinical management, and outcomes of patients with cancer. The study population included adult patients (≥ 18 years) diagnosed with ND-AML between January 1st, 2013 - December 31st, 2021. Patients were excluded if key study data were missing (i.e., date of initial AML diagnosis or date of outcome or last visit). First-line treatment regimens were mapped to relevant therapeutic categories (e.g., intensive chemo [IC] w/ cytarabine, hypomethylating agent with venetoclax [HMA+ven]) and summarized across clinical and demographic patient characteristics using descriptive analyses. Results: Among a total of 2059 patients that met study criteria, distribution of first-line treatment by category is shown in Figure 1. The most common first-line treatments were IC w/ cytarabine (46.2%), followed by HMA+ven (13.1%), and decitabine (Dec) alone and azacitidine (Aza) alone (10.2% and 9.6%, respectively). Of the 951 patients who received IC w/cytarabine, 34 (3.6%) received add-on therapy with midostaurin and 26 (2.7%) received add-on therapy with gemtuzumab ozogamicin. Approximately 6.6% of the study cohort received an investigational product as part of a clinical trial as first-line therapy. Demographic and clinical characteristics and follow-up by treatment category are shown in Table 1. Relative to other regimens, a greater proportion of patients receiving upfront intensive chemotherapy were younger, had fewer observed comorbidities, and had a favorable European Leukemia Net (ELN) risk score. No clear differences in treatment patterns were seen by racial or ethnic group, other than potential underrepresentation of black/African American and Latino patients among those receiving investigational therapy. The proportion of patients treated with HMA+ven has increased over time starting in 2018, particularly in patients with ELN adverse risk, and the use of HMA alone decreased during the same time period. There was a potential decrease in use of IC w/cytarabine and a rise in use of HMA+ven during 2020. Use of single agent targeted therapies and LDAC-based therapies were relatively uncommon. Conclusions: In our cohort of patients with ND-AML, the predominant first-line treatment was an intensive chemotherapy regimen. Treatment group by year of diagnosis indicates that over time, greater proportions of patients are receiving HMA+ven as first-line intervention, predominantly among older patients and those with adverse risk per ELN stratification. This study demonstrates the capability of using RWD to characterize the ND-AML treatment landscape, particularly after the introduction of novel therapeutic agents. Findings are subject to the inherent limitations associated with observational data, including the challenges in collecting and analyzing real-world data (e.g. missing treatment data or other characteristics) which may result in bias or limited generalizability of study findings. Future research may evaluate real-world safety or effectiveness, particularly in populations underrepresented in clinical trials, to inform the post-approval therapeutic landscape. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Subclinical Minute FLT3-ITD Clone Can be Detected in Clinically FLT3-ITD-Negative Acute Myeloid Leukemia

Introduction The fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is the most common recurrent mutation in acute myeloid leukemia (AML). FLT3-ITDs are predominately located in exons 14 and 15 and affect the juxtamembrane domain (JM) of the membranous tyrosine kinase receptor. Oligoclonal FLT3-ITD clone could be detected in single patient. In patients with FLT3-ITD-positive AML, the FLT3-ITD clone could disappear in relapsed AML, the whereas some cases acquired FLT3-ITD in relapsed sample despite the fact that FLT3-ITD was absent in initial AML samples. Clinically, FLT3-ITD was detected by agarose gel or capillary electrophoresis of the polymerase chain reaction (PCR) product. The detection sensitivity of these methods is about 1-5% variant allele frequency (VAF). PCR amplicon sequence using next-generation sequencing (NGS) enabled us to detect dynamics of subclinical minute FLT3-ITD clones. We hypothesized that subclinical minute FLT3-ITD could be detected in clinically FLT3-ITD-negative AML and that the clone might contribute to the emergence of FLT3-ITD on relapse. Patients and Methods Hokkaido Leukemia Net (HLN) is prospective cohort study collecting acute leukemia samples from affiliated hospitals covering Hokkaido. In this study, we focused on cytogenetically normal (CN) AML without FLT3-ITD diagnosed by electrophoresis. Initial diagnostic samples and relapsed samples were analyzed by the NGS assay to determine whether they had minute FLT3-ITD clones. FLT3 exons 14 and 15 were PCR-amplified and deep-sequenced by Miseq (>20,000 reads). Using an FLT3-ITD-positive AML cell line (MOLM14), the limit of quantitative detection of minute FLT3-ITD was 0.0067%. We defined "minute FLT3-ITD” as one that was not detected by gel electrophoresis but was detected by NGS with VAF of more than 0.0067%. This study was conducted in accordance with the Helsinki Declaration and was approved by the institutional review boards. Results A total of 74 FLT3-ITD-negative cases were identified in 112 CN-AML cases registered in HLN from 2017 to 2019 (age range 21-93 years (median 68); 36 males and 38 females). Initial diagnostic samples were analyzed for FLT3-ITD by NGS and 28 independent minute FLT3-ITDs (VAF range: 0.0077-5.4%, median VAF:0.16%) were detected in 19 cases (25.7%). ITD lengths were 18-93 bp (median length: 44 bp), and all minute FLT3-ITDs were in-frame mutations. In 5 of the 19 cases, more than two independent minute FLT3-ITDs were detected. The number of independent ITDs ranged from 1-5 (median number:1) per patient. We compared characteristics of the patients with and those without minute FLT3-ITD. The proportion of BM specimens (89.5% vs 87.3%, P=1.0), white blood cells [23,100 (460-250,900) vs 10,700 (800-174,000), P=0.138], NPM1 mutation positivity (52.6% vs 29.1%, P=0.094), percentage of patients with primary induction failure (47.4% vs 41.8%, P=0.44), and percentage of patients who received allogenic stem cell transplantation (21.1% vs 27.3%, P=0.76) were not significantly different between the minute FLT3-ITD-positive group and the minute FLT3-ITD-negative group. On the other hand, blast percentage (83.0% vs 66.0%, P=0.033) and the rate of relapse within 1 year (36.8% vs 10.9%, P=0.031) were significantly higher in minute the FLT3-ITD-positive group, whereas overall survival rate were not different in the two groups (P=0.78). In a median period of 25 months after initial diagnosis, 22 patients relapsed [7 (36.8%) of 19 minute FLT3-ITD-positive patients and 15 (27.3%) of 55 minutes FLT3-ITD-negative patients]. Of those 22 cases, we collected 23 relapse specimens of 18 cases [1st relapse (rel1), 18; 2nd relapse, (rel2), 5]. FLT3-ITD became clinically positive in 2 cases in rel1 and in 2 cases in rel2 (Figure, red lines). Regarding rel1, 2 of 3 cases in the initial minute FLT3-ITD-positive group developed clinically relevant FLT3-ITD, while none of the 15 cases in the minute FLT3-ITD-negative group developed clinically relevant FLT3-ITD (P=0.020). In both rel1 and rel2, cases that developed clinically positive FLT3-ITD (filled circle) were positive for minute FLT3-ITD at the preceding time point (empty circle). Conclusion This is the first study clarifying the clonal dynamics of minute FLT3-ITD in clinically FLT3-ITD-negative AML. The clinical significance of an FLT3 inhibitor for patients with minute FLT3-ITD needs to be clarified in the future. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Life Satisfaction and Quality of Life in AML Long-Term Survivors: Primary Results of the AMLCG-Survivorship Study

Introduction An increasing proportion of patients with acute myeloid leukemia (AML) become long-term survivors (AML-LTS). Somatic and psycho-social outcomes are therefore becoming increasingly important, but little is known about the long-term effects of the disease and its treatment. Methods We designed a comprehensive analysis of AML survivorship outcomes including psycho-social well-being and somatic health status, and conducted a questionnaire-based study collecting data from long term survivors and their physicians. This report focuses on general and health-related life satisfaction (gLS/hrLS, measured by the FLZ-M questionnaire). Compared to quality of life (QoL), LS takes into consideration the subjective importance of various areas of life, and the participant's satisfaction with each. Impact of anxiety and depression, incidence of secondary cancer as well as clonal hematopoiesis are reported separately (Görlich et al, Moret et al, Krauss et al). We compared LS of AML-LTS with normative data of German adults not diagnosed with AML. Participants' FLZ-M scores were standardized relative to age- and sex-stratified normal population means and standard deviations. Results 427 former AML patients who had been enrolled in AMLCG clinical trials (AMLCG-1999/-2004/ -2008) or the AMLCG patient registry participated in this study between 5 and 18.6 years [y] after their initial AML diagnosis (median, 11.3y). Median age of AML-LTS was 61y (range 28y-93y), and 56% were female. Thirty-eight percent of participants had been treated with chemotherapy alone, while 62% received at least one allogeneic stem cell transplant (HSCT). A relapse had occurred in 24% of participants. Unexpectedly, the gLS summary score (median, .12) was significantly higher in AML-LTS (p<.001) compared to controls (median, 0), although differences were small (95%CI .03 - .32) and very likely not clinically relevant (difference and CI < 1SD). No significant difference was found for health-related life satisfaction (hrLS). Looking at LS subscales, AML-LTS reported significantly lower satisfaction with hobbies (median, -.24), fitness (median, -.18) and composure (median, -.41), but higher satisfaction with finances (median, .36), living situation (median, .10), family life (median, .37), energy (median, .04), mobility (median, .56) and independence (median, .71; all p<.003). Notably, subgroups of participants reported poor hrLS (>1SD below control mean; 17.5%) or poor gLS (13.5%), while 26% reported poor overall QoL as reported previously. All three outcomes are correlated (r=.63 to .76), with the closest association observed between QoL and hrLS (Figure A). To identify factors associated with poor LS, we fitted logistic regression models including pre-specified cofactors (age, sex, time since initial diagnosis, relapse and alloHSCT) and additional variables that associated with LS in univariate analyses. Risk of poor gLS was increased with younger age, male sex, smaller household size and income, higher depression scores and low social support (Table 1). Factors associated with poor hrLS were previous treatment with chemotherapy alone, female sex, lower number of children, high anxiety and fatigue scores, and high comorbidity burden (Table 1). Participants with higher fatigue and anxiety scores, lower social support and higher comorbidity burden reported significantly lower QoL (Table 1). No influence on QoL was found for other characteristics including treatment (HSCT vs. no HSCT), previous relapse, or AML type (p>.05). Figure A illustrates multi-dimensional associations between risk factors and psycho-social outcomes. Discussion Unlike previous studies of AML survivorship outcomes, our large cohort included a diverse spectrum of patients regarding age, time since diagnosis, and treatment modalities, which allows for new insights into long-term quality of life and life satisfaction. Our study establishes that different factors impact overall QoL and life satisfaction in AML long-term survivors. Importantly, general life satisfaction of AML long-term survivors seems not to be influenced by treatment related factors or somatic comorbidities after AML. Our data suggest AML and its treatment can have long-term psycho-social and somatic health effects, but many former patients nevertheless are satisfied with their overall life situation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

S301: GERMAN AMLCG-SURVIVORSHIP STUDY: QUALITY OF LIFE AND LIFE SATISFACTION IN AML LONG-TERM SURVIVORS

Background: An increasing proportion of patients with acute myeloid leukemia (AML) become long-term survivors. Somatic and psycho-social outcomes in survivors are therefore becoming increasingly important, but little is known about the long-term effects of the disease and its treatment. Aims: The primary aim of this study was to compare quality of life (QoL, measured by the FACT-G questionnaire) and general and health-related life satisfaction (gLS/hLS, measured by the FLZ-M questionnaire) of AML-LTS with normative data of German adults who were not diagnosed with AML. Methods: We designed a comprehensive analysis of AML survivorship outcomes including psycho-social well-being and somatic health status and conducted a questionnaire-based study collecting data from AML long term survivors (AML-LTS). This report focuses on overall and health-related quality of life. Somatic morbidity in AML-LTS is reported separately (Moret et al.). Results: 427 former AML patients who had been enrolled in AMLCG trials (AMLCG-1999, AMLCG-2004, AMLCG-2008) or the AMLCG patient registry, participated in this study between 5 and 18.6 years (y) after their initial AML diagnosis (median, 11.3y). Median age of AML-LTS was 61y (range 28y-93y), and 56% were female. Thirty-eight percent of participants had been treated with chemotherapy alone, while 62% received at least one allogeneic stem cell transplant (alloHSCT). A relapse occurred in 24% of the participants. Unexpectedly, age- and sex-normalized quality of life and general life satisfaction summary scores were significantly higher in AML-LTS (p<.001) compared to adults without the diagnosis of AML. Raw score points of AML-LTS on the FACT-G summary scale also were higher than in age and sex-matched normal adults by a median of 4.7 points (95% CI: 2.82 – 7.2) – a differences that likely is clinically not relevant, considering an established cutoff for clinical relevance of 7 raw score points. No difference between AML-LTS and normal adults was found for health-related life satisfaction (hLS). Using the cutoff for clinical importance (i.e., 7 points below age- and sex-matched population norm), 26.1% of participants reported relevant impairment of overall QoL. To identify factors potentially associated with poor overall QoL, we constructed a logistic regression model including pre-specified cofactors (age, sex, time since initial diagnosis, relapse and alloHSCT) and additional covariables that associated with QoL in univariate analyses (Figure 1). We found that participants with no children, lower educational level, shorter time since diagnosis and altered financial situation reported significantly lower QoL. No influence was found for disease- and treatment related factors including treatment (alloHSCT vs. no alloHSCT), previous relapse, or de novo vs secondary or therapy-related AML. Image:Summary/Conclusion: Unlike previous studies of AML survivorship, our large cohort included a diverse spectrum of patients regarding age, time since diagnosis, and treatment modalities, which allows for new insight into long-term QoL. Our study establishes that overall QoL in AML long-term survivors is comparable to the general population, with further improvement from five years post diagnosis onwards. Importantly, disease- and treatment-related factors, such as prior relapse or alloHSCT, are not associated with overall QoL. However, we were able to identify risk factors for worse QoL, delineating a subgroup of patients that may still have a need for targeted psycho-social interventions five or more years after an AML diagnosis.

Autologous hematopoietic stem cell transplantation followed by interleukin-2 for adult acute myeloid leukemia patients with favorable or intermediate risk after complete remission.

High-dose chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) is generally the optimal option for patients with acute myeloid leukemia (AML). However, for favorable- and intermediate-risk patients, the regimen remains less understood due to graft versus host disease (GVHD) and increased non-relapsed mortality (NRM) caused by allo-HSCT. Additionally, the benefit of maintenance therapy has not yet been conclusively proven. Here, we conducted a retrospective study on the long-term outcome of AML patients with favorable or intermediate risk who underwent autologous hematopoietic stem cell transplantation (auto-HSCT) followed by interleukin-2 (IL-2) subcutaneous injection as maintenance therapy. A total of 49 patients from 2007 to 2019 were included in our study. They all received a daunorubicin + cytarabine regimen as induction chemotherapy followed by four to six cycles of consolidation therapy with medium- or high-dose cytarabine. Once patients achieved complete remission (CR1), they started receiving auto-HSCT followed by IL-2 injections. The results showed that no patients stopped receiving IL-2 injections on account of adverse side effects, and the 5-year overall survival (OS) and leukemia-free survival (LFS) rates were 85.6 ± 5.0% and 78.5 ± 6.1%, respectively. The multivariate analysis also suggested that age, gender, initial white blood cell (WBC) count, AML subtype, cytogenetic risk, and conditioning regimen did not affect the prognosis. In conclusion, auto-HSCT followed by IL-2 injection is an effective treatment that can improve the prognosis of AML for patients with favorable or intermediate risk.

Evaluating the Safety of Outpatient Ramp up of Venetoclax in Acute Myeloid Leukemia and Myelodysplastic Syndrome

IntroductionVenetoclax, a selective b-cell lymphoma 2 (BCL2) inhibitor, has changed the landscape of treatment in newly diagnosed acute myeloid leukemia (AML) elderly patients. In addition, it has shown promising efficacy in treatment-naive and relapsed/refractory (r/r) myelodysplastic syndrome (MDS) as well as r/r AML. Unique toxicities of venetoclax include tumor lysis syndrome (TLS) due to the rapid apoptotic effect by BCL2 inhibition. Although TLS is less frequently reported in AML, due to the fatalities from TLS reported in chronic lymphocytic leukemia patients, inpatient hospitalization during initial venetoclax dose ramp up is recommended. Hydroxyurea or leukapheresis can also be used to achieve a white blood cell (WBC) count of less than 25,000 prior to initiating venetoclax. At NYU Langone Health (NYULH), patients are initiated on venetoclax dose ramp up in the outpatient setting regardless of WBC count due to the low incidence of TLS. The aim of this study is to assess the safety of outpatient venetoclax dose escalation in our AML and MDS patients.Methods/ResultsThis was an institutional review board approved, descriptive, retrospective medical chart review of 60 adult patients who received venetoclax dose ramp up in the outpatient setting at NYULH and NYU Long Island from March 1, 2017 to March 01, 2021. Patients were included if they were 18 years and older, received venetoclax in combination with either hypomethylating agents (HMA) or low-dose cytarabine in the outpatient setting, and had a documented diagnosis of either de novo AML, r/r AML, newly diagnosed high-risk MDS, or r/r MDS. The primary endpoint was the number of patients demonstrating laboratory or clinical TLS as defined by Cairo-Bishop Criteria described by Howard and colleagues. Secondary endpoints included hospital admission within two weeks of initiating venetoclax therapy. If patients did not have laboratory values obtained within one week of starting venetoclax, but had continued hematology follow-up with the NYU health system, it was assumed that these patients did not experience laboratory or clinical TLS.One patient was counted as two individual patients because venetoclax was initiated as initial frontline AML treatment, followed by re-trial for relapsed disease. The median age was 74 years (IQR, 66-83). Most patients (24) had newly diagnosed AML (40%) followed by 17 patients (28.3%) with newly diagnosed MDS, 14 patients (23.3%) with r/r AML, and 5 patients (8.3%) with r/r MDS. The median total WBC count prior to initiating venetoclax was 2.25 x 10^3 cells/uL (IQR, 1.40-7) with a median blast count in the bone marrow of 25% (IQR, 11.5-53). Two patients had an initial WBC count of greater than 25. Thirty-six (60%) patients had a Carlson Comorbidity Index score of 5 or greater.Decitabine was the most common combination agent used (50%), followed by azacitidine (48.3%), and low-dose cytarabine (1.7%). The majority of patients, 39 (65%) were prescribed the standard dosing ramp up schedule, with 15 patients (25%) had venetoclax initiated during cycle two or thereafter. Thirty-seven (61.7%) patients ramped up to the full venetoclax dose (either 400mg or 600mg). The most common reasons for dose reductions included drug-drug interactions (7 patients), neutropenia or anemia (7 patients), and general tolerance (5 patients). Thirty-seven (61.7%) patients were prescribed allopurinol prophylaxis. No patients received rasburicase prior to initiating venetoclax.Only 1 patient (1.67%) experienced both laboratory and clinical tumor lysis and required intravenous hydration in outpatient clinic. Three additional patients (5%) required TLS directed treatment, but did not meet TLS definition. Of note, 8 patients (13.3%) did not have any laboratory values checked between days 1-7 of starting venetoclax. No patients were hospitalized within two weeks of venetoclax initiation due to TLS.ConclusionAdministering venetoclax dose ramp up in the outpatient setting avoids need for hospitalization and appears to be safe in patients with AML and MDS. Limitations of this study include the heterogeneous population and the retrospective nature of the study. Although 35% of our patients were not prescribed the standard venetoclax ramp up dose, this highlights the existing challenges of treating elderly AML and MDS patients. DisclosuresAbdul Hay: Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Speakers Bureau. OffLabel Disclosure:To assess the safety of outpatient venetoclax ramp up in both newly diagnosed & relapsed/refractory acute myeloid leukemia & myelodysplastic syndrome

Quality of Life and Life Satisfaction in AML Long-Term Survivors: Primary Results of the AMLCG-Survivorship Study

IntroductionAn increasing proportion of patients with Acute Myeloid Leukemia (AML) become long-term survivors. Somatic and psycho-social outcomes are therefore becoming increasingly important, but little is known about the long-term effects of the disease and its treatment.MethodsWe designed a comprehensive analysis of AML survivorship outcomes including psycho-social well-being and somatic health status and conducted a questionnaire-based study collecting data from AML long term survivors (AML-LTS) and their physicians. This report focuses on overall and health-related quality of life. Somatic, especially cardiovascular, morbidity in AML-LTS are reported separately (Moret et al.). The primary aim of this study was to compare quality of life (QoL, measured by the FACT-G questionnaire) and general and health-related life satisfaction (gLS/hLS, measured by the FLZ-M questionnaire) of AML-LTS with normative data of German adults who were not diagnosed with AML (Holzner et al. 2009; Daig et al. 2009). FLZ-M and FACT-G scores were standardized relative to the normal population mean and standard deviation, stratified by sex and age. These z-scores were then tested against the fixed value 0 (indicating no difference between AML-LTS and the general population) using Mann-Whitney U-tests. Our statistical design incorporated a sequentially rejective testing procedure to maintain the multiple testing significance level at 5%, using a graphical model as described by Bretz et al. (2009).Results427 former AML patients who had been enrolled in AMLCG trials (AMLCG-1999, AMLCG-2004, AMLCG-2008) or the AMLCG patient registry, participated in this study between 5 and 18.6 years [y] after their initial AML diagnosis (median, 11.3y). Median age of AML-LTS was 61y (range 28y-93y), and 56% were female. Thirty-eight percent of participants had been treated with chemotherapy alone, while 62% received at least one allogeneic stem cell transplant (alloSCT). A relapse occurred in 24% of the participants.Unexpectedly, quality of life and general life satisfaction summary scores were significantly higher in AML-LTS (p<.001) compared to adults without the diagnosis of AML, although most differences on QoL subscales relative to the general population were small and very likely not clinically relevant. No statistical difference between AML-LTS and normal adults was found for health-related life satisfaction (hLS).Notably, a subgroup of participants (26%) reported poor physical well-being (PWB), indicated by a FACT PWB subscore more than one standard deviation (SD) below the age- and sex-matched general population value (Figure A). This resulted in poor overall QoL (i.e. >1 SD below normal) for 13% of the participants (Figure B).To identify factors potentially associated with poor overall QoL, we constructed a logistic regression model including pre-specified cofactors (age, sex, time since initial diagnosis, relapse and alloSCT) and additional covariables that associated with QoL in univariate analyses (Table C). We found that participants with younger age, male sex, lower educational level, shorter time since diagnosis and a altered financial situation reported significantly lower QoL. No influence was found for other characteristics including treatment (alloSCT vs. no alloSCT), previous relapse, or de novo vs. secondary or therapy-related AML.DiscussionUnlike previous studies of AML survivorship, our large cohort included a diverse spectrum of patients regarding age, time since diagnosis, and treatment modalities, which allows for new insight into long-term quality of life. Our study establishes that overall QoL in AML long-term survivors is comparable to the general population. Improvement of QoL continues beyond five years post diagnosis. Importantly, disease- and treatment-related factors, such as prior relapse or status post allogeneic transplantation, are not associated with overall QoL. However, we were able to identify risk factors for worse QoL (younger age, male sex, alteration of the financial situation), delineating a subgroup of patients that may still have a need for targeted psycho-social interventions five or more years after an AML diagnosis. [Display omitted] DisclosuresBerdel: Philogen S.p.A.: Consultancy, Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees. Hiddemann: Janssen: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Metzeler: AbbVie: Honoraria; Astellas: Honoraria; Daiichi Sankyo: Honoraria; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy; Pfizer: Consultancy; Celgene/BMS: Consultancy, Honoraria, Research Funding.

Molecular Response Patterns in Relapsed/Refractory AML Patients Treated with Selinexor and Chemotherapy

Molecular Response Patterns in Relapsed/Refractory AML Patients Treated with Selinexor and Chemotherapy

AML with germline DDX41 variants is a clinicopathologically distinct entity with an indolent clinical course and favorable outcome.

Germline DDX41 variants in myeloid neoplasms (MNs) are not uncommon, and we explored the prevalence and characterized the clinical and pathologic features in a cohort of 3132 unrelated adult MN patients. By targeted next-generation sequencing, we identified 28 patients (20 men and 8 women) with pathogenic germline DDX41 variants who developed acute myeloid leukemia (AML), in which only 3 (11%) had a family history (FH) of MNs. A subacute clinical course of cytopenia (mean duration of 11.2 months, range 0-72 months) prior to the initial AML diagnosis was accompanied by a low blast count (median at 30%, range 20-70%) in hypocellular marrows (93% of all patients), in vast contrast to the typical proliferative subtypes of AML in the elderly. Most patients had a normal karyotype (75%) and acquired a second DDX41 variant (69%). A favorable overall survival (OS) was observed in comparison to that of common subtypes of AML with wild-type DDX41 in age-matched patients. Our study demonstrated that the frequent germline pathogenic DDX41 variants characterized a clinically distinct AML entity. Features characteristic of DDX41-mutated AML include male predominance, often lack of FH, indolent course, low proliferative potential, frequent somatic DDX41 variants, and a favorable OS.

Outcomes of Patients With Acute Myeloid Leukemia Who Relapse After 5 Years of Complete Remission.

Leukemia relapse 5 years after achieving first complete remission (CR1) is uncommon in patients with acute myeloid leukemia (AML). In this study, we evaluated the outcomes of AML patients with late relapse at our institution and reviewed the literature for these patients. The study cohort consisted of nine AML patients with late relapse. The median interval between CR1 and AML relapse was 6.1 years (range: 5.1–16.2 years). At relapse, the karyotype was different from the initial AML diagnosis in 50% of patients. At the time of AML relapse, seven patients received induction chemotherapy and two patients received hypomethylating agents with an overall CR rate of 66%. The median time to relapse after achieving second CR (CR2) was 16.5 months [95% confidence interval (CI): 9.4, NA]. The median overall survival after first relapse was 28.6 months (95% CI: 7.3, 3.4–66.5 months). Despite initial CR after reinduction therapy, relapse rates are still high, suggesting that alternative strategies for postremission therapies are warranted in CR2. These approaches include the use of allogeneic hematogenic cell transplantation and the use of newly approved AML agents as maintenance therapy in nontransplant eligible patients.

Second Relapse of Pediatric Patients with Acute Myeloid Leukemia: A Report on Current Treatment Strategies and Outcome of the AML-BFM Study Group

BACKGROUND: Children with acute myeloid leukemia (AML) still experience high rates of relapse. Facing increasing survival after first relapse, it appears critically important to examine the consequences of a second relapse in more detail. However, there is no population-based data available in pediatric AML and no reliable statement about general survival, patients' characteristics or treatment approaches can be made. Herein, we report current survival results following second relapse from the BFM study group, which represents to our knowledge the largest available dataset for this subgroup of patients. PATIENTS AND METHODS: Between 2004 and 2017, 1222 pediatric patients (age less than 18 years at initial AML diagnosis) with AML (no secondary leukemia, no Down syndrome, no acute promyelocytic leukemia) were registered in the population-based AML-BFM registry and trials in Germany, Austria, Czech Republic and Switzerland providing a longitudinal data collection with treatment, response rates, survival and disease characteristics. Central review of source documentation confirmed accuracy and consistency of all reported data. Only patients with a documented date of first and second complete remission (CR1 and CR2) and a diagnosed second relapse until the age of 21 are included. Statistical analyses were performed with SAS version 9.4 (SAS Institute). All living patients were censored at the time of last follow-up, but no patient later than 03/27/2020. The median follow-up after diagnosis of second relapse was 6,5 years. RESULTS: In all registered patients, 7% (83 out of 1222) met the strict criteria for a second relapse. For further analyses patients with a date of second relapse diagnosis after 12/31/2017 (n=6), two patients with isolated CNS relapse, who did not receive systemic chemotherapy, one patient with an underlying syndrome and one patient with insufficient data have been excluded. The median age at second relapse was 9,2 years. Sixty percent (n=44) of the patients, who experienced a second relapse, did so within a year after first relapse diagnosis. Eighty percent (n=58) and 7% (n=5) had one or two previous HSCTs, respectively. Eighty-nine percent (n=65) received an anthracycline-containing re-induction (DNX-FLA) followed by FLA or another intensive treatment regimen before at first relapse. In contrast to the standardized treatment approaches in first relapse, patients with second relapse received a wide range of therapy. Forty-six patients (63%) have been treated with an intensive cytotoxic treatment (Table 1). Seventeen patients (23%) got palliation only. Among the 25 patients (35%) who proceeded to HSCT, 21 patients (88%) had a prior HSCT. Survival after second relapse was very poor with a 5-year pOS of 15±4% (see Figure 1A) and a considerable cumulative incidence of early deaths (until day 56 after diagnosis: CI ED 19±5%). Prognosis did not improve over time with consistent overall survival rates until 2017 (see Figure 1B). Causes of death include disease progression (n= 51, 70% of all patients), a combined SCT-related and disease-related cause (n=3, 5%) and SCT-related complications (n=4, 4%) or treatment-associated toxicity (n=5, 7%). The 5-year pOS was 2±2% for patients with an early second relapse vs. 33±9% for those experiencing a second relapse more than a year after the first. (p&amp;lt;0.0001; Figure 1C). The timing of a first relapse and age did not show any influence on overall survival. The best response achieved in the respective bone marrow sample after up to two cycles with cytotoxic treatment have been categorized. Out of 45 patients with conclusive data 31.1% (n=14) achieved a third CR with a pOS of 36±13%, while 62.2% of the patients showed a nonresponse to the treatment (n=28, pOS 7±5%) or no evidence of leukemia, but also no peripheral regeneration (6.7%, n=3, pOS 0±0%). CONCLUSION: These data provide new insights into treatment strategies, prognostic factors and outcome of children with second relapse in pediatric AML. As expected, survival is poor, but nonetheless possible in this increasingly relevant subgroup of patients. These data may serve as foundation for urgently needed international clinical trials for relapsed and refractory AML in children. Disclosures Bourquin: Servier: Other: Travel Support. Reinhardt:CLS Behring: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Roche: Research Funding; bluebird bio: Membership on an entity's Board of Directors or advisory committees.

Streamline - Retrospective Cohort Study of Relapsed or Refractory (R/R) FLT3-Mutated Acute Myeloid Leukemia (AML): Real-World Treatment, Testing Patterns, and Outcomes

Streamline - Retrospective Cohort Study of Relapsed or Refractory (R/R) FLT3-Mutated Acute Myeloid Leukemia (AML): Real-World Treatment, Testing Patterns, and Outcomes

Efficacy, Safety, and Pharmacokinetics (PK) of Azacitidine (AZA) in Children and Young Adults with Acute Myeloid Leukemia (AML) in the Phase 2 AZA-AML-004 Trial

Efficacy, Safety, and Pharmacokinetics (PK) of Azacitidine (AZA) in Children and Young Adults with Acute Myeloid Leukemia (AML) in the Phase 2 AZA-AML-004 Trial

Post-Remission Treatment (Tx) Patterns for Patients (Pts) with Newly Diagnosed (ND) Acute Myeloid Leukemia (AML) in the Connect® MDS/AML Disease Registry

Post-Remission Treatment (Tx) Patterns for Patients (Pts) with Newly Diagnosed (ND) Acute Myeloid Leukemia (AML) in the Connect® MDS/AML Disease Registry

Salvage Therapy Outcomes in a Historical Cohort of Patients With Relapsed or Refractory Acute Myeloid Leukemia

BackgroundThe prognosis of patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) is poor, with no universal standard salvage therapy currently available for most patients. Novel therapies with efficacy in patient subsets often have limited activity in alternative subsets, resulting in a majority of patients not gaining benefit from these therapies. This study systematically evaluated patient outcomes in a large cohort of R/R AML patients from a single institution across all salvage therapy lines, up to and including the third line. Patients and MethodsOutcomes of R/R AML patients treated at a single institution (MD Anderson Cancer Center, Houston, TX) between 2002 and 2016 were entered into a central database. Eligible patients received one or more lines of salvage therapy after first occurrence of R/R AML. Patients who received second- or third-line salvage treatment were also included in the first salvage analysis. Eligible patients were ≥ 18 years old at time of initial AML diagnosis, with no central nervous system involvement. ResultsA total of 818 eligible patients received one or more lines of salvage therapy, 809 received second-line salvage therapy, and 397 received third-line salvage therapy. Complete remission rates decreased from 14% after first salvage therapy to 9% after second salvage therapy and 3% after third salvage therapy. Median overall survival was 6.30, 4.07, and 2.98 months after first, second, and third salvage therapies, respectively. ConclusionThese data indicate that the best chance of obtaining long-term remission in AML is with a successful first induction. Strategies that improve initial response and decrease the likelihood of relapse should be pursued.