Initial Acute Myeloid Leukemia Diagnosis Research Articles

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.

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.

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.

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.

SRSF2 or TET2 Mutations in Patients with MDS Predict Increased Red Blood Cell Alloimmunization

INTRODUCTION: Chronic inflammation is associated with increased red blood cell (RBC) alloimmunization. Patients with sickle cell disease (SCD), systemic lupus erythematosus and inflammatory bowel disease, all conditions with increased levels of inflammation, have been shown to be more alloimmunized when compared to the general population. High prevalence rates of RBC alloimmunization have also been observed in patients with myelodysplastic syndrome (MDS). It has recently been shown that an inflammatory microenvironment may be a key driver of MDS pathogenesis. There are a few specific genes recurrently mutated in MDS that have been found to be associated with activation of the innate immune system and formation of the inflammasome, including some involved in epigenetic modification - ASXL1, DNMT3A, EZH2 and TET2 - and spliceosome formation - SF3B1, SRSF2 and U2AF1. The aim of this study was to determine if the genetic mutations driving the inflammatory milieu in MDS could simultaneously be creating an environment that promotes alloimmunization. PATIENTS AND METHODS: We identified patients diagnosed with a myeloid neoplasm, including patients with MDS and acute myeloid leukemia (AML), between 2015 and 2020 on whom a type and screen had been ordered. We recorded the patients’ primary diagnosis, sex, race/ethnicity, age at first sequencing, somatic mutations identified by next generation sequencing (NGS), blood type, antibody screen results, specific alloantibodies and autoantibodies identified, and number of RBC and platelet units transfused. Patients with an autoantibody, a clinically significant alloantibody, or non-specific reactivity with a potential antibody under investigation on their screen were put in the positive antibody screen category, and those with reactivity solely due to Rh immune globulin or monoclonal antibody therapy were put in the negative antibody screen category. Univariate logistic regression was run separately for patients initially diagnosed with AML and those initially diagnosed with a non-AML myeloid neoplasm (MN), using sex, age, race/ethnicity, number of RBC units transfused, and somatic mutation, to determine if any of these variables had a significant association with a positive antibody screen. If quasi-complete separation issues existed, Firth's method for separation was applied to the logistic regression model. All analyses were conducted using a 95% confidence level. RESULTS: Seventy-six patients met inclusion criteria; 44 were male and 32 were female, and ranged in age from 14 to 89 years. The majority of patients were Caucasian (n = 64). Thirty-three patients had an initial diagnosis of AML; 43 were initially diagnosed with a MN, including MDS (n = 36), myeloproliferative neoplasm (n = 2), chronic myelomonocytic leukemia (n = 4) and chronic myeloid leukemia (n = 1). Number of RBC units transfused ranged from 3 - 112 in patients with AML and 0 - 131 in patients with a MN. Thirteen patients with AML had a positive antibody screen (39.4%), compared to 21 patients with a MN (48.8%). Patients with AML most often developed an alloantibody without an accompanying autoantibody (58.3%), while patients with a MN most often developed alloantibodies in addition to autoantibodies (52.4%). Patients with a MN and a SRSF2 mutation had a significantly increased rate of allo- or auto-immunization as compared to patients with AML and a SRSF2 mutation (p-value = 0.035). Similarly, patients with a MN and a TET2 mutation had a significantly increased rate of allo- or auto-immunization as compared to patients with AML and a TET2 mutation (p-value = 0.021). CONCLUSIONS: In patients with a MN, the presence of a SRSF2 or TET2 mutation predicted the presence of at least one allo- or autoantibody. Our data support the hypothesis that genetic mutations involved in formation of the inflammasome may be involved in the increased alloimmunization seen in patients with MDS. Our study of alloimmunization in MDS, and further studies like it, may enable us to predict based on genetic mutations which patients with MDS may be at increased risk for becoming alloimmunized. Similar to prophylactic C, E and K antigen matching that some blood banks employ in patients with SCD to minimize formation of alloantibodies, extended phenotype matching for the most immunogenic antigens could also be considered in patients with MDS and SRSF2 or TET2 mutations to decrease alloimmunization in this patient population.

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

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

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.

Outcomes of TP53‐mutated AML with evolving frontline therapies: Impact of allogeneic stem cell transplantation on survival

Outcomes of <scp><i>TP53</i></scp>‐mutated <scp>AML</scp> with evolving frontline therapies: Impact of allogeneic stem cell transplantation on survival

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

Myeloid Sarcoma Reveals a Unique Tumor Micro-Environment and Differential Prognosis Based on Transplant Status and Type of Treatment Received

BackgroundMyeloid sarcoma (MS) is the rare extramedullary proliferation of myeloid blasts that disrupts the normal architecture of various tissues in patients with Acute myeloid leukemia (AML). MS can present concurrently with untreated AML or present as relapsed AML. Based on our clinical observations and emerging immune checkpoint inhibitor (ICI) studies in AML (Davids et al NEJM 2016), MS appears to behave differently based on transplant status and tends to have better ICI sensitivity. One of the prominent mechanisms of relapse post-transplant is immune escape via the loss of leukemia recognition by the graft. This is mediated by down regulation of HLA expression. We hypothesize that the immune signatures in the bone marrow (BM) microenvironment are distinct from those from the local MS microenvironment. Thus, we aimed to comprehensively explore the MS microenvironment at single-cell level, providing clues for more effective therapies including ICI, and insights into the molecular pathogenesis, clinicopathological features and outcomes of MS.MethodsThis is an investigator-initiated study where we collected paired fresh MS tissues and BM samples from patients with MS as well as retrospective collection of paired MS and BM samples that are already sectioned and paraffin-embedded. Eligible patients were consentable adults > 18 years old and have MS lesions whether at diagnosis or at relapse of their AML disease. We excluded patients who have multiple malignancies or patients who are unable to provide samples. Accepted samples are 10-millimeter tissue or 1 million cells per milliliter. The fresh samples were cryopreserved and used for single cell RNA sequencing and ex vivo immune cellular assays. The sectioned tissues were used for multiplex immunohistochemical staining (mIHC) that tested a panel of 6 antibodies (CD3, CD68, CD4, CD33, PDL-1 and HLA-DR). We sought to further perform spatial transcriptome analysis (Visium) that complements mIHC for in-depth characterization of the MS microenvironment and immunopathogenesis. The clinical and genomic annotations for these samples were abstracted from the patients' charts. We have utilized Next generation sequencing (NGS) panels that interrogated 24- 180 oncogenes, including FLT3, IDH, CALR, NPM1, KRAS, NRAS, and TP53. Survival estimates using K-M curves and multivariate analysis were performed via SPSS.ResultsOur study recruited 30 patients so far. Mean age at diagnosis was (57.6 ± 14 years); 63.3% of the patients were males (n=19) and 80% of the patients were Caucasian (n=24). In our cohort, 46.6% of the patient had MS diagnosed as the cause of relapse after stem cell transplant (n=14) while the rest had MS at the initial diagnosis of AML. The most common cytogenetic abnormality in our cohort was complex karyotype in 30% of the patients. Molecular landscape of MS at diagnosis and relapse was done in 90% of the patients and shown in figure 1A,B. MS conferred a poor prognosis if diagnosed on initial presentation vs a new presentation at relapse post stem cell transplant with a median OS (4 months vs 25 months p 0.003) (HR 3.9 - 95% CI 1.4-11.1) figure 2. Interestingly, we have noticed that patients who received Venetolcax based therapies have poor prognosis compared to other therapies (IDH/FLT3 inhibitors, conventional chemotherapies, or ICI); median OS (9.3 months vs 24 months p 0.02) (HR 3.9 - 95% CI 1.2-12.6) figure 3. In a prelim analysis using validated mIHC, we have observed abundant HLA-DR expression in both blast cells and nonmalignant stromal cells of the MS microenvironment (n=4) figure-4. By contrast, PD‐L1 was expressed mainly on a number of stromal cells rather than blast cells in the MS microenvironment. Further special localization analysis of tumor immune infiltrates (TILs) is being conducted to disclose clinical outcomes and biological significance of PD-L1, HLA-DR and TILs in MS. Spital transcriptomics are in process and will be presented.ConclusionMS diagnosed concurrently with untreated AML appears to confer a poor prognosis and behave differently than MS diagnosed as relapse post-transplant. MS appears to be resistant to Venetoclax based therapies and patients tends to do worse on this therapy. In contrast to BM microenvironment, blast cells within MS appears to have abundant expression of HLA-DR in both neoplastic tumor cells and nonmalignant stromal cells promoting immune recognition which might explain their sensitivities to ICI. [Display omitted] DisclosuresAbaza: BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dinner: Pfizer: Consultancy, Honoraria; Kite/Gilead: Consultancy, Honoraria. Altman: Glycomimetics: Other: data monitoring committee; ALX Oncology Inc.: Research Funding; Loxo: Research Funding; ImmunoGen: Research Funding; Abbvie: Honoraria, Research Funding; Amgen: Research Funding; Aprea: Research Funding; Astellas: Honoraria, Research Funding; Aptos: Research Funding; Boehringer Ingelheim: Research Funding; Celgene: Research Funding; Syros: Membership on an entity's Board of Directors or advisory committees; Fujifilm: Research Funding; Biosight: Membership on an entity's Board of Directors or advisory committees, Other: reimbursement for travel, Research Funding; Kura Oncology: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kartos Therapeutics: Research Funding.

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.

Extramedullary Infiltration in Pediatric Acute Myeloid Leukemia on Surveillance Magnetic Resonance Imaging and its Relationship With Established Risk Factors.

Purpose:Extramedullary infiltration (EMI) is a rare condition defined by the accumulation of myeloid tumor cells beyond the bone marrow. The clinical significance is still controversial. This study was aimed to evaluate the incidence, characteristics, and prognostic significance of EMI on complete magnetic resonance imaging (MRI) investigation in newly diagnosed pediatric acute myeloid leukemia (AML) patients who are asymptomatic without clinical evidence to suspect EMI.Materials and Methods:Retrospective clinical and radiologic review of 121 patients with MRI examination at the time of initial diagnosis of AML without any clinical evidence suggestive of EMI was performed. Patients were divided into 2 groups according to the presence or absence of EMI, and the relationship between EMI and established risk factors was analyzed. Initial white blood cell count, the occurrence of an event (including relapse, death, and primary refractory disease), survival status, and detailed information on cytogenetic/molecular status was performed by a thorough review of electronic medical records system. All patients underwent full imaging evaluation with the contrast-enhanced whole body and some regional MRI at the time of initial diagnosis.Results:The median age at diagnosis was 10.77 years (range, 0.37 to 18.83 y). Based on the risk stratification system of AML, 36, 45, and 40 patients are classified as low-risk, intermediate-risk, and high-risk groups, respectively. MRI at the time of the initial diagnosis of AML revealed 35 of 121 patients (28.9%) with EMI. The most common site of EMI was a skull, followed by the lower extremity bone and meninges of the brain. The median age at diagnosis was significantly younger in patients with EMI (7.87 vs. 11.08 y, P=0.0212). Low incidence of FLT3/ITD mutation, low incidence of AML-ETO gene rearrangement, and the larger extent and more severe degree of bone marrow involvement was related with EMI. However, there was no significant prognostic difference in event-free survival and overall survival regardless of the presence of EMI in the overall patient population and each risk group. The location of EMI occurrence was also not related to prognosis.Conclusions:Even if EMI symptoms are not evident, surveillance MRI scans at the initial diagnosis of pediatric AML patients are very helpful in detecting a significant number of EMIs. Younger age, some molecular features, and more severe bone marrow involvement of AML patients were related with EMI. However, there was no significant prognostic difference between patients with or without EMI regardless of risk group. Further prospective investigation is necessary to validate the prognostic effect of EMI in a larger group of patients with different risk groups.

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.

Myelodysplastic syndrome with t(6;9)(p22;q34.1)/DEK-NUP214 better classified as acute myeloid leukemia? A multicenter study of 107 cases.

t(6;9)(p22;q34.1)/DEK-NUP214 is a recurrent genetic abnormality that occurs in 1-2% of patients with acute myeloid leukemia (AML), and rarely in myelodysplastic syndrome (MDS). It has been suggested by others that all myeloid neoplasms with t(6;9)/DEK-NUP214 may be considered as AML, even when blast count is <20%. In this study, we compared the clinicopathologic features of 107 patients with myeloid neoplasms harboring t(6;9)/DEK-NUP214: 33 MDS and 74 AML. Compared with patients with AML, patients with MDS were older (p = 0.10), had a lower white blood cell count (p = 0.0017), a lower blast count in the peripheral blood (p < 0.0001) and bone marrow (p < 0.0001), a higher platelet count (p = 0.022), and a lower frequency of FLT3-ITD mutation (p = 0.01). In addition, basophilia was not a common feature in the patients of this cohort. Although there was no difference in overall survival between MDS and AML patients (p = 0.18) in the entire cohort, the survival curves did show a trend toward favorable survival in MDS patients. Multivariate analyses showed that initial diagnosis of MDS vs. AML and allogeneic hematopoietic stem cell transplantation were prognostic factors for survival of patients with t(6;9)/DEK-NUP214 (p = 0.008 and p < 0.0001, respectively). Our data suggest that MDS with t(6;9)/DEK-NUP214 is prognostically not equivalent to AML with t(6;9)/DEK-NUP214. These data also show that stem cell transplantation greatly improves the survival of MDS and AML patients with myeloid neoplasms associated with t(6;9)/DEK-NUP214.

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