Partnership For Health Analytic Research Research Articles

When are breakthrough therapies cost-effective?

BACKGROUND: An increasing proportion of novel drug approvals use accelerated pathways, with notable growth in the US Food and Drug Administration-designated breakthrough pathway in recent years. Breakthrough therapy (BT) designation suggests that these therapies offer substantial potential to improve health outcomes but their value for money is not fully understood, as BTs typically cost more than non-BTs (NBTs). OBJECTIVE: To assess the economic value of BTs and factors associated with their reported value. METHODS: Using the Tufts Medical Center Cost-Effectiveness (CE) Analysis Registry, we (1) summarized the CE of BTs, as measured by cost per quality-adjusted-life-year (QALY); (2) compared the CE of BTs and NBTs in the United States; and (3) identified factors associated with BT CE using general estimating equation models across US willingness-to-pay (WTP) benchmarks ($50K-$150K/QALY). RESULTS: Between 2013 and 2018, the US Food and Drug Administration approved 279 drugs, designating 83 (32%) as BTs. Incremental costs and health gains (QALYs) were higher for BTs relative to NBTs ($29,000 vs $20,000 and 0.7 vs 0.2 QALYs, respectively), and BTs had more favorable CE ratios compared with NBTs (median values $38,000/QALY vs $50,000/QALY, respectively). For BTs, hepatitis C treatments had the most favorable CE ratios, which may be driven by the curative nature of some hepatitis C therapies. Furthermore, BT CE ratios for new molecular entities (NMEs) were about 40% lower than ratios for non-NME BTs on average, which may signal more value for money when the BT has a new active molecule. Regression analysis to identify trends driving CE found that BT drugs compared with active comparators (instead of best supportive care) were less likely to be cost-effective at standard US WTP thresholds (odds ratio [OR] = 0.1-0.6) and that BTs in the neoplasm space also trended less likely to be cost-effective (OR = 0.12-0.43). CE ratios reported by studies with industry funding were also more likely to be cost-effective than ratios from studies with other funding sources (OR = 4.3-4.5), though this finding was not significant at WTP thresholds over $50,000/QALY gained. CONCLUSIONS: Evidence from published, peer-reviewed CE studies suggests that BTs may confer greater health benefits than NBTs in terms of overall QALYs. Our analysis supports that the US Food and Drug Administration BT designation may be associated with increased value for money for these BTs. However, factors such as the disease area, NME status, and comparator (active vs standard of care) will also influence whether these therapies are cost-effective. DISCLOSURES: Dr Cohen reports grants or contracts from PhRMA Foundation, National Pharmaceutical Council, AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, Gilead Sciences, Regeneron, Pfizer, Merck, Johnson & Johnson, Vir Biotechnology, Moderna, Amgen, and Lundbeck; consulting fees from AbbVie, Biogen, IQVIA, Novartis, Partnership for Health Analytic Research, Pharmerit, Precision Health Economics, Sage, Sanofi, and Sarepta; and stock or stock options from Bristol-Myers Squibb, Johnson & Johnson, and Merck. Ms Kowal is an employee and stockholder of Genentech, Inc. Dr Yeh is an employee and stockholder of Roche, Inc.

Antifibrotic therapies reduce mortality and hospitalization among Medicare beneficiaries with idiopathic pulmonary fibrosis.

BACKGROUND: Additional real-world studies are needed to more fully elucidate the effectiveness of antifibrotic treatment in slowing the progression of idiopathic pulmonary fibrosis (IPF). OBJECTIVE: To compare mortality and hospitalization between Medicare beneficiaries with IPF who initiate antifibrotic therapy and those who did not receive treatment. METHODS: A retrospective observational study of Medicare beneficiaries using the 100% Medicare Research Identifiable File was conducted. We included patients aged 67 years and over diagnosed with IPF (≥ 1 inpatient or ≥ 2 outpatient claims with IPF diagnosis) during the study period (January 1, 2010-December 31, 2017). Patients who initiated antifibrotic treatment (pirfenidone or nintedanib) between October 15, 2014 (FDA approval date) and December 31, 2017 (ie, treated patients) were compared with those who did not receive treatment during a historical period (January 1, 2012-October 14, 2014) before the availability of antifibrotics (ie, untreated historical controls). Patients were matched by propensity score, and the outcomes, mortality, and hospitalization (all cause and respiratory related) were compared using a Cox proportional hazards model. RESULTS: We identified 4,641 treated patients and 4,641 propensity score-matched controls who met all study criteria; 352 treated patients who lacked matches were excluded from the study. Cox regression analysis of treated patients vs matched controls showed a significantly lower risk of mortality (HR = 0.62, 95% CI = 0.57-0.68); lower risk of hospitalization (HR = 0.71, 95% CI = 0.67-0.76; HR = 0.70, 95% CI = 0.64-0.76); and lower rate in number of hospitalizations per month (incident rate ratio [IRR] = 0.65, 95% CI = 0.60-0.71; IRR = 0.65, 95% CI = 0.58-0.73). CONCLUSIONS: This study suggests that treatment with antifibrotics may confer a survival benefit and protection against all-cause and respiratory-related hospitalization for IPF patients. DISCLOSURES: This work was sponsored by F. Hoffmann-La Roche/Genentech, Inc. Corral is employed by Genentech, Inc. Reddy, Chang, Broder, and Gokhale are employed by Partnership for Health Analytic Research LLC, a health services research company, which was hired by Genentech to conduct this research. Mooney has received advisory board/consulting fees and research support from Genentech, unrelated to this work. Mooney also reports advisory board/consulting fees and research support from Boehringer Ingelheim; personal fees from Imvaria; and grants from Celgene and Pliant, unrelated to this work. Through their employment with Partnership for Health Analytic Research, Reddy, Chang, Broder, and Gokhale have been compensated to conduct research for AbbVie, Akcea, ASPC, Amgen, AstraZeneca, BMS, Boston Scientific Corporation, Celgene, Eisai, Ethicon, GRAIL, Helsinn, Illumina, Innovation and Value Initiative, Ionis, Jazz, Kite, Novartis, Otsuka, Pathnostics, PhRMA, Prothena, Sage, Verde Technologies, Genentech, Inc., Greenwich Biosciences, Inc., Mirum Pharmaceuticals, Inc., Sanofi US Services, Inc., Sunovion Pharmaceuticals, Inc., and Dompe US, Inc., unrelated to this work. This research was presented as an abstract at CHEST 2020 Annual Meeting (virtual), October 18-21, 2020, and American Thoracic Society 2020 Virtual Meeting, June 2020.

Healthcare Resource Utilization and Costs of Patients with AL Amyloidosis: An Analysis of Hospitalizations in the Premier Database

Healthcare Resource Utilization and Costs of Patients with AL Amyloidosis: An Analysis of Hospitalizations in the Premier Database

Dasatinib Treatment Patterns after Pleural Effusion Among Patients with Chronic Myeloid Leukemia

Dasatinib Treatment Patterns after Pleural Effusion Among Patients with Chronic Myeloid Leukemia

Thrombosis Prophylaxis with Apixaban in Patients Treated with Asparaginase

Thrombosis Prophylaxis with Apixaban in Patients Treated with Asparaginase

Poor Outcomes of Older Adults with Acute Promyelocytic Leukemia (APL) Regardless of Insurance Types

IntroductionPrior studies report multiple factors, including insurance status, as significant barriers to healthcare access in the United States. Barriers to healthcare access may lead to worse outcomes in APL, which requires timely diagnosis and prompt treatment. We performed a large database analysis to examine the effects of insurance type and other factors on one-month mortality and overall survival (OS) in patients ≥65 years of age with APL.MethodsWe aimed to compare one-month mortality and OS of patients on private insurance with patients on non-private insurance, which included Medicare, Medicaid, and other government insurance. Patients ≥65 years of age who were diagnosed with APL between 2004-2015 were identified from the National Cancer Database (NCDB). Multiple regression analysis was used to evaluate the effects of insurance type on the probability of one-month mortality. The Kaplan-Meier method estimated overall survival (OS), which was defined as the time from APL diagnosis to last contact or death from any cause. We used Cox regression model to determine the effects of insurance type on mortality risk adjusting for the other covariates of interest.ResultsWe analyzed a total of 1520 patients- either private (12%) or non-private (88%), which included Medicare (85%), Medicaid (2%), and other government insurance (1%). Among total patients, 60% were 65-74 years of age, 46% were female, 87% were white, 84% had Charlson-Deyo comorbidity index (CCI) of 0 or 1, and 52% were treated at academic centers.One-month mortality was 18% for patients with private insurance and 23% for patients with non-private insurance. In a multivariate regression analysis, insurance type did not affect one-month mortality (Table 1). One-month mortality was higher for older patients; patients ≥75 years of age were more likely to die at one month compared to patients 65-74 years (Odds ratio [OR] 1.98, 95% confidence interval [CI] 1.53-2.57, p<0.0001). Compared to patients with CCI of 0, patients with CCI of 1 (OR 1.91, 95% CI 1.43-2.55, p<0.0001), CCI 2 (OR 1.68, 95% CI 1.10-2.56, p=0.01), and CCI ≥3 (OR 2.88, 95% CI 1.75-4.73, p<0.0001) had worse one-month mortality. One-month mortality was higher for patients treated at comprehensive community cancer center compared to those treated at academic cancer center.Median follow-up for surviving patients was 4.5 years (0.03-13.72). Three-year OS was 56% for private insurance and 50% for non-private insurance (Table 2, Figure 1). In Cox proportional hazard model, there was no statistically significant difference in OS based on insurance type. (Table 3). OS did decrease with increasing age. Compared to patients 65-74 years of age, the likelihood of death was higher for patients ≥75 years (Hazard ratio [HR] 1.80, 95% CI 1.57-2.07, p><0.001). OS decreased with increasing comorbidities: HR 1.31 (95% CI 1.12-1.54, p=0.0007) for CCI 1, HR 1.60 (95% CI 1.28-1.99, p<0.0001) for CCI 2, and HR 1.80 (95% CI 1.37-2.37, p<0.0001) for CCI ≥3 compared to patients with CCI of 0. OS was lower for patients treated at comprehensive community cancer center compared to those treated at academic cancer center. Higher income status and diagnosis after 2009 were associated with improved OS.ConclusionIn our large database analysis, while insurance types were not associated with mortality in patients ≥65 years of age with APL, one-month mortality (about 20%) still remains high and only half of older adults are alive at 3 years. Our study highlights a significant effect of increasing age on mortality even among older adults, with approximately 2-fold higher risk of mortality among patients ≥75 years versus those 65-74 years. Other factors associated with higher mortality included treatment outside of academic centers and lower income status. Unlike younger adults, APL in older adults still has significant unmet need. [Display omitted] DisclosuresGundabolu: Bristol-Myers Squibb Company: Consultancy; Blueprint Medicines: Consultancy; Pfizer: Research Funding; Samus Therapeutics: Research Funding; BioMarin Pharmaceuticals: Consultancy. Bhatt: Servier Pharmaceuticals LLC: Consultancy; Partnership for health analytic research, LLC: Consultancy; Abbvie: Consultancy, Research Funding; Jazz: Research Funding; Incyte: Consultancy, Research Funding; Pfizer: Research Funding; Tolero Pharmaceuticals, Inc: Research Funding; National Marrow Donor Program: Research Funding; Abbvie: Consultancy, Research Funding; Genentech: Consultancy; Rigel: Consultancy.

Efficacy of Autologous Stem Cell Transplantation in Adult Burkitt/ Burkitt-like Lymphoma: A Systematic Review

Introduction: Burkitt and Burkitt-like lymphoma (BL/BLL) are highly proliferative germinal or post-germinal B cell tumors. Few studies have evaluated the impact of autologous stem cell transplantation (ASCT) on disease outcomes. We performed a systematic review to analyze the efficacy of ASCT in upfront consolidation and for treatment of relapsed/ refractory cases in adult BL/BLL.Methods: A systematic search of the electronic database (PubMed, Cochrane, Google Scholar, and EMBASE) was conducted for relevant studies. Any clinical trial, prospective study, or retrospective study with clear outcome measures on the efficacy of ASCT in adult patients with BL/BLL were eligible for inclusion. The overall survival (OS), progression-free survival (PFS), complete response (CR), partial response (PR), and progression or relapse were used to assess the efficacy.Results: For patients who underwent ASCT in first CR, 5-year PFS and OS ranged between 70-78% and 70-83%, respectively. For relapsed/refractory disease, 5-year PFS and OS were reduced at 27% and 31%, respectively. Patients undergoing ASCT for chemoresistant disease fared poorly with an OS of 7% at 3 years versus 37% for chemosensitive disease (p ≤ 0.00001). The overall response rate (CR or PR) to ASCT for patients transplanted in first CR ranged between 71% and 92%. This was reduced to 37% for patients who were transplanted in disease status other than first CR. Disease progression/relapse was observed in 16% to 29% of the patients transplanted in first CR, and 55% to 60% in relapsed disease.Conclusion: Our systematic review found insufficient evidence to support ASCT over chemotherapy alone in the first remission for adult BL/BLL. Evidence supports guidelines recommending ASCT for chemosensitive disease but suggests there is no benefit to ASCT for chemoresistant disease. Prospective studies of ASCT are required to definitively understand the value of ASCT for BL/BLL. [Display omitted] DisclosuresBhatt: Pfizer: Research Funding; Tolero Pharmaceuticals, Inc: Research Funding; Incyte: Consultancy, Research Funding; Jazz: Research Funding; Abbvie: Consultancy, Research Funding; Partnership for health analytic research, LLC: Consultancy; Servier Pharmaceuticals LLC: Consultancy; Rigel: Consultancy; National Marrow Donor Program: Research Funding; Abbvie: Consultancy, Research Funding; Genentech: Consultancy.

Association of Insurance Types and Survival in Acute Promyelocytic Leukemia (APL)

IntroductionHealth insurance, or lack thereof, is a significant barrier to health care access in the United States. Patients without insurance or with inadequate coverage are more likely to delay or forego treatment, even with acute illness or significant symptoms, leading to worse health outcomes. We aimed to analyze if insurance types impacted one-month mortality and overall survival (OS) in younger patients with APL.MethodsWe utilized National Cancer Database to identify patients <65 years who were diagnosed with APL between 2004-2015. We used multiple logistic regression analysis to evaluate the effects of insurance type on the probability of one-month mortality. OS was estimated by the Kaplan-Meier method. A full Cox regression model was used to determine the effects of insurance types on mortality.ResultsA total of 5380 patients were included. Median age was 44 years (0-64), 50% were female, 93% had Charlson-Deyo comorbidity index (CCI) of 0 or 1, and 58% were treated at academic centers. Insurance types included private (67%), Medicaid or other government insurance (19%), Medicare (7%) or uninsured (6%). Patients with Medicare were older and had increased comorbidities. Lower percent of patients with Medicare (23%) or Medicaid/Other government insurance (21%), compared to those with private insurance (56%) or uninsured patients (63%) were treated at academic centers.One-month mortality was higher for patients with Medicare (16%) or uninsured patients (14%), compared to those with Medicaid/Other government (8%) or private insurance (7%).Patients with Medicare (Odds ratio [OR] 1.69, 95% confidence interval [CI] 1.23-2.32, p=0.001) or uninsured patients (OR 2.23, 95% CI 1.56-3.18, p<0.0001) had worse one-month mortality compared to those with private insurance (Table 1). One-month mortality worsened with increasing comorbidities (OR 2.31 for CCI 1, OR 4.44 for CCI 2, and OR 7.02 for CCI ≥3 compared to patients with CCI of 0, p<0.0001). Female patients and patients traveling <6 miles to the treatment center had lower one-month mortality.Median follow-up for surviving patients was 5.4 years (0.008-13.9). Three-year OS was 89% for private insurance, 81% for Medicaid/Other government insurance, 63% for Medicare, and 80% for uninsured patients (Table 2, Figure 1). Patients with Medicaid/Other government insurance (hazard ratio [HR] 1.39, 95% CI 1.19-1.63 p<0.0001), and Medicare (HR 1.88, 95% CI 1.57-2.24, p<0.0001) were associated with worse OS compared to patients with private insurance (Table 3). Compared to patients ≤18 years of age, the likelihood of death was worse for patients 41-64 years (HR 0.68, 95% CI 1.47-4.90, p=0.001). OS worsened with increasing comorbidities (HR 1.71 for CCI 1, HR 2.33 for CCI 2, and HR 3.48 for CCI ≥3 compared to patients with CCI of 1, p<0.0001). Male gender (p=0.0002) was associated with decreased OS.ConclusionIn one of the largest database analyses, we identified insurance status as a significant factor affecting one-month mortality and OS in APL. Our results revealed a higher one-month mortality but similar longer-term OS in uninsured patients compared to patients with private insurance, which may reflect poor access to healthcare necessary for prompt diagnosis and timely initial treatment; similar longer-term OS may reflect a higher proportion of younger patients with less comorbidities in uninsured group. Patients with Medicaid/Other government or Medicare insurance had worse OS compared to private insurance. The reasons for worse OS may be multifactorial including problems with access to quality leukemia care or drug coverage, or the effects of other differences in the patient population including income and in case of Medicare patients, older age and comorbidity burden. Our results raise concern for healthcare disparities based on insurance types and highlight challenges associated with improving OS in patients with Medicaid, Medicare, or no insurance, which comprise a significant proportion of patients with APL. [Display omitted] DisclosuresGundabolu: Samus Therapeutics: Research Funding; Pfizer: Research Funding; BioMarin Pharmaceuticals: Consultancy; Blueprint Medicines: Consultancy; Bristol-Myers Squibb Company: Consultancy. Bhatt: Genentech: Consultancy; Abbvie: Consultancy, Research Funding; National Marrow Donor Program: Research Funding; Tolero Pharmaceuticals, Inc: Research Funding; Pfizer: Research Funding; Incyte: Consultancy, Research Funding; Jazz: Research Funding; Abbvie: Consultancy, Research Funding; Partnership for health analytic research, LLC: Consultancy; Servier Pharmaceuticals LLC: Consultancy; Rigel: Consultancy.

Minimal Toxicity Seen When Pembrolizumab Is Added to Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia and Persistently Detectable Minimal Residual Disease: Early Results from an Ongoing Phase II Trial (ECOG-ACRIN EA9171)

Minimal Toxicity Seen When Pembrolizumab Is Added to Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia and Persistently Detectable Minimal Residual Disease: Early Results from an Ongoing Phase II Trial (ECOG-ACRIN EA9171)

Outcomes of Patients with Budd-Chiari Syndrome and Factors Predicting the Need for TIPS & Liver Transplantation - a Single-Center Long-Term Experience

Background: Budd-Chiari Syndrome (BCS) is a complex thrombotic disorder caused due to obstruction of hepatic venous outflow involving anywhere from small hepatic venules to the entrance of inferior vena cava into the right atrium. This leads to venous stasis and ischemic injury of hepatic parenchyma and sinusoids, with the risk of liver failure. The prognosis of patients with BCS had improved significantly with long-term anticoagulation and measures like Trans-Jugular-Intrahepatic-Porto-Systemic shunt (TIPS) and liver transplantation. We report the outcomes of patients who follow in our hematology practice and describe the factors predicting the need for TIPS/Liver Transplant.Methods: After appropriate Investigational Review Board permission, we identified patients with a history of BCS following in our thrombosis clinical practice from the year 2010 onwards. We evaluated their laboratory, demographic, anticoagulation data, Model of End-stage Liver Disease (MELD) score, Child-Pugh (CP) score at diagnosis or when earliest available, and other relevant clinical information as outlined. Descriptive statistics with medians, quartiles, frequencies, and percentages are reported. Further, we compared the two categories of patients who needed TIPS/Liver transplants versus those who did not. SAS version 9.4 was used for analysis. For continuous variables, a univariate nonparametric Mann-Whitney test was used. The Fisher's Exact Test was used to associate each variable with the need for TIPS/Liver Transplant.Results: Our study included 23 patients with baseline characteristics, including median age of 36 years (11-59 years), 91% whites, 61% females, 44% smokers, 61% obese(median BMI 29.9 kg/m 2), 6 of 14 women on oral contraceptive pills, 22% with thrombosis history, 17% with stroke history, median hemoglobin 13.4 gm/dL(8.9-20 gm/dL), white blood cell count 9,400/L (3,050-31,500/L), platelet count 294,000/L(14,000-767,000/L), serum creatinine 0.87 mg/L (0.55-2.52 mg/dL), total protein 6.3 gm/dL (5.2-8.8 gm/dL), Bilirubin 2.1 mg/dL(0.1-20.2 mg/dL), Aspartate Aminotransferase (AST) 61 U/L(16-1037 U/L), Alanine Aminotransferase (ALT) 43U/L(18-1694 U/L), MELD score 15 (range 7-38), CP score 9 (5-14), 74% with cirrhosis, 82% with ascites at one point, 57% with myeloproliferative neoplasm (MPN), 4.3% with Paroxysmal Nocturnal Hemoglobinuria (PNH), 17% with Antiphospholipid antibodies positive (APS), 13% had positive antinuclear antibodies, 35% needed TIPS and 44% required liver transplantation. 57% with Janus Kinase (JAK2) V617F mutation (1 patient with a low variant allele frequency of 1%), 1 patient (4.3%) had Calreticulin (CALR) mutation positive MPN, 91% remained on long-term anticoagulation with 40% using warfarin, 35% apixaban, 9% Enoxaparin or Rivaroxaban for long-term anticoagulation, 13% developed heparin-induced thrombocytopenia (HIT). 8.7% had developed BCS after Ad26.COV2.S vaccine to prevent SARS-CoV-2 infection. Excluding the patients with missing variables, 5 of 12 had Protein C deficiency, 3 or 10 had Protein S deficiency, 8 of 20 with Antithrombin (AT) deficiency, 4 of 14 with heterozygous factor V Leiden mutation, 0 of 10 with prothrombin gene mutation, 1 of 13 with hyper-homocysteinemia. 35% had gastrointestinal bleeding though 65% of patients had evidence of varices by endoscopy. When the group needing TIPS/Liver transplant/died is compared to those who did not, they had higher bilirubin, MELD, PC score, AT deficiency, cirrhosis, ascites, and JAK2 mutation (p-value significant: Table 1). With a median follow-up of 90 months, overall survival was not statistically significant between the two groups (Figure 1). Two patients (8.7%) died out of a total of 23.Conclusions: Our data indicate that in patients with BCS, neoplasms (61%), particularly MPN (57%), are very commonly diagnosed. Compared to the historical data in patients with BCS with dismal prognosis (60-80% six-month mortality rate), the overall survival had significantly improved, likely due to supportive measures like TIPS/Liver transplant and long-term anticoagulation. Outside the established variables like CP and MELD, lower antithrombin activity and positive JAK2 mutation status also predicted a higher TIPS/Liver transplant need. [Display omitted] DisclosuresBhatt: Partnership for health analytic research, LLC: Consultancy; Abbvie: Consultancy, Research Funding; Jazz: Research Funding; Incyte: Consultancy, Research Funding; Pfizer: Research Funding; Tolero Pharmaceuticals, Inc: Research Funding; National Marrow Donor Program: Research Funding; Abbvie: Consultancy, Research Funding; Genentech: Consultancy; Servier Pharmaceuticals LLC: Consultancy; Rigel: Consultancy. Gundabolu: BioMarin Pharmaceuticals: Consultancy; Blueprint Medicines: Consultancy; Bristol-Myers Squibb Company: Consultancy; Pfizer: Research Funding; Samus Therapeutics: Research Funding.

Healthcare Utilization and Costs in Commercially Insured Patients with AL Amyloidosis

Objectives: Amyloid light chain (AL) amyloidosis is a rare, progressive, and typically fatal disease caused by extracellular deposition of misfolded immunoglobulin light chains (LCs). Soluble toxic aggregates and deposited fibrils (amyloid) lead to progressive failure of vital organs, including the heart, kidneys, and nervous system, causing significant morbidity and mortality. Its effects on resource utilization are poorly understood. The aim of this study was to estimate healthcare utilization and costs among patients with AL amyloidosis.Methods: In this cross-sectional study, for each calendar year (CY) 2007-2015, patients with AL amyloidosis were identified in the Truven MarketScan® Commercial and Medicare Supplemental databases if they had: (1) ≥1 inpatient or 2 outpatient claims consistent with AL amyloidosis [International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes: 277.30 or 277.39; International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes: E85.4x, E85.8x, or E85.9x] in any diagnosis field within that CY; and (2) AL treatment (eg, chemotherapy, hematopoietic stem cell transplant [HSCT]) following diagnosis. This algorithm was used to identify patients as there is no diagnosis code specific to AL amyloidosis. Exclusion criteria were age <18 and lack of enrollment on January 1 of ID year. Full-year enrollment was not required after exploratory analysis suggested most patients with partial year enrollment likely died during the year. We reported descriptive statistics on healthcare costs and utilization by CY and overall. Some patients may have been included in multiple CYs at different points in the course of their disease. Costs were adjusted to 2015 US$. All analyses were done using SAS®.Results: There were 7,326 patients identified overall (between 368 and 1,080 unique patients per year), with a mean (SD) age 63.6 (12.1), 45% of whom were female. All US regions were represented. Hospitalization was common: 50.1% (n=3,670) were admitted at least once during the year and 11.3% (827) were admitted 3 or more times. Utilization decreased over time (57.0% in 2007 and 46.2% in 2015 had any hospital admission). Among admitted patients, mean (SD) length of stay (LOS) was 14.7 (19.5) days; 3.7% of patients had HSCT, with mean (SD) LOS of 21.0 (12.6) for the transplant. Patients were seen for outpatient care with a mean (SD) of 45.2 (36.2) times per year. Mean (SD) [median] total annual cost was $101,855 (148,965) [51,939] for all patients. Medical costs were $88,801 (144,491) [38,936], with $50,126 (86,232) [22,100] accrued in the outpatient setting, $37,909 (100,892) [802] inpatient, and $766 (3,650) [0] emergency department. Outpatient pharmacy costs were $13,054 (26,606) [3,501]. Costs increased over time ($92,866 in 2007 to $114,030 in 2015).Conclusions: Patients with AL amyloidosis use substantial healthcare resources. Half of patients with AL amyloidosis were admitted to the hospital each year for an average stay of more than 2 weeks. Visits to laboratories, offices, and other outpatient sites occur almost twice a month. The total cost of this care is more than $100,000 per patient per year and rising. New therapies aimed at improving organ response have the potential to reduce disease burden and healthcare utilization. DisclosuresQuock:Prothena Biosciences Inc: Employment, Other: Stockholder. Yan:Partnership for Health Analytic Research, LLC: Employment. Chang:Partnership for Health Analytic Research, LLC: Employment. Broder:Partnership for Health Analytic Research, LLC: Employment.

Epidemiology of AL Amyloidosis in a US Commercially Insured Population

Introduction: Amyloid light chain (AL) amyloidosis is a rare, progressive, and typically fatal disease caused by extracellular deposition of misfolded immunoglobulin light chains. There is a paucity of epidemiological studies of AL amyloidosis, and many existing studies are not recent. The objective of the current study was to provide an up-to-date estimate of the prevalence and incidence of AL amyloidosis in the US.Methods: This was a retrospective, cross-sectional study using 2007-2015 data from the Truven MarketScan® Commercial and Medicare Supplemental claims databases. As there is no diagnosis code specific to AL amyloidosis, the following algorithm was used to identify patients. Adults ≥18 years old with AL amyloidosis were identified if they (1) had at least one inpatient claim or two outpatient claims consistent with AL amyloidosis [International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes: 277.30 or 277.39; International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes: E85.4x, E85.8x, or E85.9x] in any diagnosis field within each calendar year and (2) received one AL-specific treatment (eg, chemotherapy, hematopoietic stem cell transplant [HSCT]) on or after the first amyloidosis diagnosis in the study period. Prevalence was calculated as the number of AL patients divided by the number of enrollees on June 30 of each calendar year and reported as per million person-years (PMPY). Incidence was calculated as the number of patients with AL amyloidosis who were disease free and enrolled in a health plan for 1 year prior, divided by the number of enrollees enrolled from July 1 of the previous year to June 30 of each calendar year and reported as PMPY. A sensitivity analysis requiring enrollees to have continuous enrollment in each calendar year (and in the year prior for incident cases) found similar estimates.Results: Between 2007 and 2015, 7,326 prevalent patients with AL amyloidosis were identified, ranging from 368 to 1,080 cases per year. The mean (SD) age of prevalent cases was 63 (12) years and was stable from 2007 to 2015. The prevalence of AL amyloidosis increased significantly during the study period: from 15.5 in 2007 to 40.5 cases PMPY in 2015, an annual percentage change (APC) of 12% (P < 0.001) (Figure 1). The incidence of AL amlydoisis ranged from 9.7 to 14.0 cases PMPY, with no statistically significant increase (APC:3.1%; P= 0.114) (Figure 2). Prevalence and incidence were generally higher in males than females.Conclusion: The pattern of an increase in AL amyloidosis prevalence, coupled with stable incidence, is consistent with earlier diagnosis over time that extends life, although our study could not determine whether this mechanism was responsible for the observed change. Our database included commercially insured patients only and so may not precisely reflect the US population. Cases were identified using claims, not clinical methods, which might overestimate or underestimate prevalence and incidence. Nonetheless, extrapolating from these data, there are at least 12,000 adults in the US currently living with AL amyloidosis, and the number seems likely to rise in the future. [Display omitted] DisclosuresQuock:Prothena Biosciences Inc: Employment, Other: Stockholder. Yan:Partnership for Health Analytic Research, LLC: Employment. Chang:Partnership for Health Analytic Research, LLC: Employment. Broder:Partnership for Health Analytic Research, LLC: Employment.

Real-World Burden of Comorbidities in US Patients with AL Amyloidosis

Introduction: Amyloidlight chain (AL) amyloidosis is a rare, progressive, and typically fatal disease caused by extracellular deposition of misfolded immunoglobulin light chains (LCs). The toxic LC aggregates and deposited fibrils (amyloid) in AL lead to progressive failure of vital organs, including the heart, kidneys, and nervous system. The objective of this study was to estimate the burden of comorbidities among patients with AL amyloidosis in a real-world setting.Methods: This was a retrospective, cross-sectional study using 2007-2015 data from the Truven MarketScan® Commercial and Medicare Supplemental claims databases. As there is no diagnosis code specific to AL amyloidosis, the following algorithm was used to identify patients. For each calendar year (CY), adult patients ≥18 years old with AL amyloidosis were identified if they (1) had at least one inpatient claim or two outpatient claims consistent with AL amyloidosis [International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes: 277.30 or 277.39; International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes: E85.4x, E85.8x, or E85.9x] in any diagnosis field and (2) received AL-specific treatments (eg, chemotherapy, hematopoietic stem cell transplant [HSCT]) on or after the first AL amyloidosis diagnosis in the study period. Full-year enrollment was not required after exploratory analyses suggested most patients with partial year enrollment likely died during the year. Descriptive statistics were reported by CY and overall. Some patients may have been included in multiple CYs at different points in the course of their disease. All analyses were done using SAS®.Results: A total of 7,326 patients with AL amyloidosis were included in the study period (between 368 and 1,080 unique patients per year). The mean (SD) age of the total population with AL amyloidosis was 63.6 (12.1) years old and 45% were female. All US regions were represented. The most common AL-related comorbidities were renal disease (39.3%), congestive heart failure (33.2%), and moderate or severe liver disease (28.6%). Other common comorbidities include hyperlipidemia (45.7%), moderate or severe liver disease (28.6%), any malignancy/lymphoma/leukemia excluding multiple myeloma (23.4%), monoclonal gammopathy of undetermined significance (19.6%), diabetes without chronic complications (18.3%), hypothyroidism (17.7%), and hypotension (16.2%). At least one claim with a diagnosis of multiple myeloma was identified in 38.9% of patients. The burden of comorbidities increased over time (eg, the mean (SD) of Charlson Comorbidity Index: 4.2 (3.2) in 2007 and 4.6 (3.2) in 2015.Conclusions: Patients with AL amyloidosis have a substantial burden of comorbidities. Many of the observed comorbidities, including congestive heart failure, renal disease, and liver disease, likely represent manifestations of the disease process. In summary, our current study is the first comprehensive report of the real-world burden of comorbidities in a large US population with AL amyloidosis. Physician awareness of these comorbidities may lead to better diagnosis, disease management, and treatment of AL amyloidosis. DisclosuresQuock:Prothena Biosciences Inc: Employment, Other: Stockholder. Yan:Partnership for Health Analytic Research, LLC: Employment. Chang:Partnership for Health Analytic Research, LLC: Employment. Broder:Partnership for Health Analytic Research, LLC: Employment.

Tapering Thrombopoietin Receptor Agonists in Primary Immune Thrombocytopenia: Recommendations Based on the RAND/UCLA Modified Delphi Panel Method

Tapering Thrombopoietin Receptor Agonists in Primary Immune Thrombocytopenia: Recommendations Based on the RAND/UCLA Modified Delphi Panel Method

A Phase II Study of CPX-351 As a Novel Therapeutic Approach for Patients with Myelodysplastic Syndromes (MDS) after Hypomethylating Agent Failure

Treatment options are limited for patients (pts) diagnosed with MDS at the time of hypomethylating agent (HMA) failure. One goal is to introduce another line of therapy to reduce tumor burden and enable patients to undergo hematopoietic stem cell transplant (HSCT), which may prolong survival for a subset. CPX-351, has shown better overall response rates and improved overall survival in patients with acute myeloid leukemia with underlying MDS changes compared to 7+3, suggesting that CPX-351 can be used in an MDS patient population. We hypothesized that treating MDS pts, who were failed by HMAs or were intolerant with CPX-351 would overcome HMA resistance. This is a phase II study of single agent CPX-351 administered at the standard FDA approved dose of 44 mg/m2 (daunorubicin 44 mg/m2 and cytarabine 100 mg/m2) intravenously on days 1, 3, 5 of the induction cycle. If patients achieve complete remission (CR), marrow CR, partial remission or hematologic improvement per 2006 IWG criteria they will be eligible to continue on to consolidation therapy, which consists of CPX-351 at a dose of 15.4 mg/m2 (daunorubicin 15.4 mg/m2 and cytarabine 35 mg/m2) every 28 days. Pts can receive up to 4 cycles of consolidation therapy in the absence of toxicity. The primary objective of the trial is to evaluate the efficacy of CPX-351 as measured by overall response rate (ORR) by IWG 2006 criteria. Secondary objectives include: ,1) determine the time to response (TTR), 2) evaluate the duration of response (DOR), 3) evaluate the event-free survival and the overall survival probability during trial period. Pts are risk stratified into lower vs higher-risk prior to enrollment using the Post-HMA model (Nazha A, et al. Hematologica 2016). Eligibility includes: pts &amp;gt;18 years with primary or secondary resistance to HMA, ECOG performance status &amp;lt; 2 and adequate organ function. Pts are excluded if they have uncontrolled infection or active malignancy. A total of 18 pts will be enrolled to each arm (lower and higher risk). To date, three pts were enrolled. One with MDS refractory to HMA who achieved complete remission and proceeded with 4 cycles of consolidation. The pt remained in remission 6+ months after the completion of consolidation. Another patient achieved a marrow CR but had a fungal pneumonia and then was taken off the trial (patient choice for going to hospice). The third patient had MDS/MPN, completed induction and achieved stable disease with improvement in platelets and neutrophils. All patients were lower-risk per the stratification model. No unexpected toxicity was observed. In conclusion, preliminarily CPX-351 is effective in MDS patients after HMA failure who are eligible to receive intensive chemotherapy. The treatment was well tolerated and toxicities were similar to what was observed in pivotal CPX-351 trials. The trial is ongoing and the results will be updated in the meeting. Disclosures Nazha: MEI: Other: Data monitoring Committee; Novartis: Speakers Bureau; Incyte: Speakers Bureau; Jazz: Research Funding. Mukherjee:Celgene/Acceleron: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; EUSA Pharma: Consultancy; Partnership for Health Analytic Research, LLC (PHAR, LLC): Honoraria; Bristol Myers Squib: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Aplastic Anemia and MDS International Foundation: Honoraria. Advani:Abbvie: Research Funding; Macrogenics: Research Funding; Glycomimetics: Consultancy, Other: Steering committee/ honoraria, Research Funding; Immunogen: Research Funding; Seattle Genetics: Other: Advisory board/ honoraria, Research Funding; Amgen: Consultancy, Other: steering committee/ honoraria, Research Funding; Kite: Other: Advisory board/ honoraria; Pfizer: Honoraria, Research Funding; Novartis: Consultancy, Other: advisory board; OBI: Research Funding; Takeda: Research Funding. Carraway:Jazz: Consultancy, Speakers Bureau; BMS: Consultancy, Other: Research support, Speakers Bureau; Stemline: Consultancy, Speakers Bureau; Takeda: Other: Independent Advisory Committe (IRC); Novartis: Consultancy, Speakers Bureau; Abbvie: Other: Independent Advisory Committe (IRC); ASTEX: Other: Independent Advisory Committe (IRC). Gerds:AstraZeneca/MedImmune: Consultancy; Incyte Corporation: Consultancy, Research Funding; Roche/Genentech: Research Funding; CTI Biopharma: Consultancy, Research Funding; Imago Biosciences: Research Funding; Sierra Oncology: Research Funding; Celgene: Consultancy, Research Funding; Gilead Sciences: Research Funding; Apexx Oncology: Consultancy; Pfizer: Research Funding. Patel:Alexion: Other: educational speaker. Sekeres:Takeda/Millenium: Consultancy; Pfizer: Consultancy; BMS: Consultancy. OffLabel Disclosure: CPX-351 in MDS

Outcomes of Therapy with Venetoclax Combined with Hypomethylating Agents in Favorable-Risk Acute Myeloid Leukemia (AML)

Outcomes of Therapy with Venetoclax Combined with Hypomethylating Agents in Favorable-Risk Acute Myeloid Leukemia (AML)

A Personalized Clinical-Decision Tool to Improve the Diagnostic Accuracy of Myelodysplastic Syndromes

Background While histo- and cytomorphological examinations are central to the diagnosis of myelodysplastic syndromes (MDS), significant inter-observer variability exists. The diagnosis can be challenging in pancytopenic patients (pts) without evidence of dysplasia and is contingent on observer expertise. We developed and externally validated a geno-clinical model that uses mutational data and peripheral blood counts/clinical variables to distinguish MDS from other myeloid malignancies. Methods Clinical and genomic data, including commercially available next-generation sequencing panels, were obtained for patients (pts) treated at the Cleveland Clinic (CC; 652 pts), Munich Leukemia Laboratory (MLL; 1509 pts), and the University of Pavia in Italy (UP, 536 pts). All patients had carried a diagnosis of MDS, chronic myelomonocytic leukemia (CMML), MDS/myeloproliferative neoplasm overlap (MDS/MPN), myeloproliferative neoplasm (MPN; either polycythemia vera, essential thrombocythemia, or myelofibrosis), clonal cytopenia of undetermined significance (CCUS), or idiopathic cytopenia of undetermined significance (ICUS). All diagnoses were established with bone marrow aspiration and according to World Health Organization 2017 criteria. The training cohort included data from CC and UP and randomly divided into learner (80%) and test (20%) cohorts. The final model was independently validated in the MLL cohort. A machine learning algorithm was used to build the model; multiple extraction algorithms were used to extract genomic/clinical variables on both the cohort and individual levels. Performance was evaluated according to the area under the curve of the receiver operating characteristic (ROC-AUC) and accuracy matrices. Results Among the 2697 pts included from all sites, the median age was 70 years [36 - 86]. Median hemoglobin (Hb) was 10.4g/dl [6.9 - 15.7], median platelet count (PLT) was 132 k/dL [14 - 722], median WBC count was 5.3 k/dL [1.4 - 49.9], median ANC was 2.8 k/dL [0.3 - 27.7], median monocyte count was 0.3 k/dL [0 - 9.9], and median lymphocyte count (ALC) was 1.1 k/dL [0.1 - 5.4], and median peripheral blast percentage 0% [0 - 8]. The most commonly mutated genes in all patients were (list top 5 genes) and among pts with MDS were SF3B1 (27%), TET2 (25%), ASXL1 (19%), SRSF2 (16%), and DNMT3A (11%); among patients with MDS-MPN/CMML, the most commonly mutated genes were MDS-MPN/CMML (TET2 46%, ASXL1 34%, SRSF2 29%, RUNX1 13%, CBL 12%) ; among patients with MPNs, the most commonly mutated genes were (JAK2 64%, ASXL1 27%, TET2 14%, DNMT3A 8%, U2AF1 7%); among patients with CCUS the most commonly mutated genes were (TET2 41%, DNMT3A 27%, ASXL1 19%, SRSF2 17%, ZRSR2 10%). The most important features for model predictions (ranked from the most to the least important) included: number of mutations detected/sample, peripheral blast percentage, AMC, JAK2 status, Hb, basophil count, age, eosinophil count, ALC, WBC, EZH2 mutation status, ANC, mutation status of KRAS and SF3B1, platelets, and gender. The final model achieved an average AUROC of 0.95 (95% CI 0.93-0.96) when applied to the test cohort and 0.93 (95% CI 0.91 - 0.94) when it was applied to the MLL cohort. The model also provides individual-level explanations for predictions, providing top differential diagnoses and individual-level explanations of how features influence a putative diagnosis (Figure 1b). Conclusions We developed and externally validated a highly accurate and interpretable model that can distinguish MDS from other myeloid malignancies using clinical and mutational data from a large international cohort. The model can provide personalized interpretations of its outcome and can aid physicians and hematopathologists in recognizing MDS with high accuracy when encountering pts with pancytopenia and with a suspected diagnosis of MDS. Disclosures Sekeres: Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda/Millenium: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees. Mukherjee:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Partnership for Health Analytic Research, LLC (PHAR, LLC): Honoraria; Bristol Myers Squib: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Aplastic Anemia and MDS International Foundation: Honoraria; Celgene/Acceleron: Membership on an entity's Board of Directors or advisory committees; EUSA Pharma: Consultancy. Gerds:Sierra Oncology: Research Funding; Imago Biosciences: Research Funding; Apexx Oncology: Consultancy; Celgene: Consultancy, Research Funding; Incyte Corporation: Consultancy, Research Funding; Roche/Genentech: Research Funding; CTI Biopharma: Consultancy, Research Funding; AstraZeneca/MedImmune: Consultancy; Gilead Sciences: Research Funding; Pfizer: Research Funding. Maciejewski:Alexion, BMS: Speakers Bureau; Novartis, Roche: Consultancy, Honoraria. Nazha:Jazz: Research Funding; Incyte: Speakers Bureau; Novartis: Speakers Bureau; MEI: Other: Data monitoring Committee.

A Longitudinal Population Level Analysis of Healthcare Resource Utilization, Comorbidity, and Survival in Idiopathic Multicentric Castleman Disease Patients

BACKGROUND: Human herpesvirus-8-negative/idiopathic multicentric Castleman disease (iMCD) is a heterogenous group of diseases characterized by proinflammatory hypercytokinemic state with a wide range of systemic manifestations ranging from generalized lymphadenopathy to death in severe cases. Limited data has shown an increased prevalence of organ dysfunction and cancers in iMCD patients either as a result of underlying disease pathophysiology or treatment received. The objective of this study was to assess the healthcare resource utilization, patterns of iMCD-related comorbidities, and survival of iMCD patients in a real-world setting. METHODS: We performed a retrospective analysis of administrative claims data for &amp;gt;30 million United States patients continuously enrolled over a three-year study period from January 1, 2017 and December 31, 2019. Patients were identified as iMCD if they had an ICD-10 diagnosis code for Castleman disease (D47.Z2) and ≥2 diagnostic codes corresponding to the minor criteria from the international evidence-based consensus diagnostic criteria for iMCD. Exclusion criteria included history of HIV, HHV-8, lymphoma, myeloma, lupus, or rheumatoid arthritis within one year of diagnosis of Castleman disease. Index diagnosis date (IDD) was defined as the first time a patient received a diagnosis for Castleman disease using the new ICD-10 code (D47.Z2) or the general code for lymphadenopathy (785.6) in ICD-9 that included Castleman disease, whichever was diagnosed first between 2006 and 2019. Included patients were followed for up to 5 years from IDD and evaluated for post-diagnosis hospitalizations, emergency room visits, hematologic malignancies, non-hematologic malignancies, thromboses, and organ dysfunction. Estimated average survival was calculated based on estimated incidence and prevalence rates for the iMCD patient population, assuming a stable incidence. RESULTS: We identified 191 iMCD patients including 109 women (57%) and 82 men (43%) with a mean age of 51 years (range: 6 - 90). The average post-diagnosis follow up was 3.2 years after IDD (range: 0.3 - 14.1). Within the first year of iMCD diagnosis, 58.9% of patients required inpatient hospitalization and 53.4% had at least one emergency room visit. Among the patients who remained enrolled after the first year, an average of 25.1% were hospitalized and 36.1% visited the emergency room during each subsequent year (Table 1). The annual rate of hospitalizations and emergency room visits for the entire database of &amp;gt;30 million patients was 9.0% and 20.6%, respectively. As shown in Table 2, the annual prevalence of iMCD-related comorbidities in this cohort was 18.2% for non-hematologic malignancies, 6.3% for hematologic malignancies (including lymphomas and myelomas from second year follow up onwards), 5.8% for thromboses, 5.7% for renal failure, and 5.2% for respiratory failure. Based on an average annual incidence of 2.45 (95% CI, 0.85 - 8.60) per million and average prevalence of 6.31 (95% CI, 3.25 - 13.05) per million, we estimated an average survival of 2.57 (95% CI, 1.59 - 4.25) years after diagnosis in this study time period. DISCUSSION: Using a large nationally representative health claims database, we identified a cohort of iMCD patients and found a high rate of hospitalizations and emergency room visits in the first five years following diagnosis. The annual prevalence of iMCD-related organ failure was approximately 5-6% primarily involving renal and respiratory systems. This study provides further evidence to support the previously reported increase in frequency of subsequent hematologic and non-hematologic malignancies in iMCD patients. In the five-year follow up period, the average estimated survival of iMCD patients was 2.57 (95% CI, 1.59 - 4.25) years after diagnosis, which is shorter than previously published average survival durations based on academic medical centers. The worse survival in this cohort may represent iMCD survival outside of academic medical centers or may reflect inaccuracies in estimated incidence and prevalence which were used to estimate average survival. Further studies are needed to compare outcomes to age-matched controls and to determine whether these adverse outcomes are broadly seen across iMCD patients or instead attributable to a smaller subset of more severe cases. Disclosures Mukherjee: Bristol Myers Squib: Honoraria; Partnership for Health Analytic Research, LLC (PHAR, LLC): Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Aplastic Anemia and MDS International Foundation: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; EUSA Pharma: Consultancy; Celgene/Acceleron: Membership on an entity's Board of Directors or advisory committees. Martin:EUSA Pharma: Current Employment. Sande:EUSA Pharma: Current Employment. Glen:HVH Precision Analytics: Current Employment. Paige:HVH Precision Analytics: Consultancy. Yarlagadda:HVH Precision Analytics: Current Employment. Fajgenbaum:EUSA Pharma: Research Funding; Janssen Pharmaceuticals: Research Funding.

Effectiveness of Second-Line (2L) Tyrosine Kinase Inhibitor (TKI) Therapy after Resistance or Intolerance to a Prior TKI in Patients with Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase (Ph+ CML-CP)

Effectiveness of Second-Line (2L) Tyrosine Kinase Inhibitor (TKI) Therapy after Resistance or Intolerance to a Prior TKI in Patients with Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase (Ph+ CML-CP)

Prognostic Impact of a Modified European LeukemiaNet (ELN) Genetic Risk Stratification in Predicting Outcomes for Adults with Acute Myeloid Leukemia (AML) Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HCT). a Center for International Blood and Marrow Transplant Research (CIBMTR) Analysis for the CIBMTR Acute Leukemia Writing Committee

Prognostic Impact of a Modified European LeukemiaNet (ELN) Genetic Risk Stratification in Predicting Outcomes for Adults with Acute Myeloid Leukemia (AML) Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HCT). a Center for International Blood and Marrow Transplant Research (CIBMTR) Analysis for the CIBMTR Acute Leukemia Writing Committee