ABSTRACT
INTRODUCTION: Patients (pts) with blood disorders are at particular risk for severe infection and death from COVID-19. Factors that contribute to this risk, including cancer treatment, have not been clearly delineated. The ASH RC COVID-19 Registry for Hematology is a public-facing, volunteer registry reporting outcomes of COVID-19 infection in pts with underlying blood disorders. We report a multivariable analysis of the impact of cancer treatment and other key variables on COVID-19 mortality and hospitalization among pts with blood cancer. METHODS: Data were collected between April 1, 2020, and July 2, 2021. All analyses were performed using R version 4.0.2. Multivariable logistic regression explored associations between mortality and seven patient/disease factors previously reported as important to COVID-19 outcome. Independent variables included: age (>60);sex;presence of a major comorbidity (defined as any of heart disease, hypertension, pulmonary disease and/or diabetes);type of hematologic malignancy;estimated prognosis of < 6 months prior to COVID-19;deferral of ICU care;and administration of cancer treatment in the previous year (excluding single agent hydroxyurea). A secondary multivariable logistic regression explored associations between the same variables and hospitalization with COVID-19. RESULTS: We included all pts in the registry with a malignant diagnosis except for 3 patients excluded based on a data sharing agreement (N=1029). Median age category was 50-59y (range <5y to > 90y). The sample was 42% female and 28% had major comorbidities. Types of hematologic malignancies were 354 (34%) acute leukemia/MDS, 255 (25%) lymphoma, 206 (20%) plasma cell dyscrasia (myeloma/amyloid/POEMS), 116 (11%) CLL, 98 (10%) myeloproliferative neoplasm (MPN). Most pts (73%) received cancer treatment during the previous year, 9% had a pre-COVID-19 prognosis of <6months, and 10% deferred ICU care. COVID-19 mortality in the entire cohort was 17%. In multivariable analyses, age > 60 (OR 2.03, 1.31-3.18), male sex (OR 1.69, 1.11 - 2.61), estimated pre-COVID-19 prognosis of less than 6 months (OR 6.16, 3.26 - 11.70) and ICU deferral (OR 10.87, 6.36 - 18.96) were all independently associated with an increased risk of death. Receiving cancer treatment in the year prior to COVID-19 diagnosis and type of hematologic malignancy were not significantly associated with death. In multivariable analyses, age > 60 (OR 2.46, 1.83 - 3.31), male sex (OR 1.34, 1.02 - 1.76), estimated pre-COVID-19 prognosis of < 6 months (OR 4.81, 2.45 - 10.50), presence of a major comorbidity (OR 1.57, 1.15 - 2.16), and cancer treatment in the previous year (OR 1.50, 1.10 - 2.06) were all independently associated with an increased risk of a severe COVID-19 requiring hospitalization. Pts with a MPN or plasma cell dyscrasia and COVID-19 were less likely to require hospitalization for COVID-19 compared to patients with CLL, leukemia/MDS, or lymphoma. CONCLUSIONS: These analyses confirm the negative impact of age > 60, male sex, pre-COVID-19 prognosis of < 6 months, and deferral of ICU care on mortality among patients with hematologic malignancy and COVID-19. We did not observe an increased risk of COVID-19 mortality among pts with COVID-19 who received blood cancer treatment in the previous year, although rate of hospitalization was higher. Pts with some hematologic malignancies (MPN, plasma cell dyscrasias), may experience less severe COVID-19 infections than others. Disclosures: Anderson: Celgene: Membership on an entity's Board of Directors or advisory committees;Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees;Gilead: Membership on an entity's Board of Directors or advisory committees;Janssen: Membership on an entity's Board of Directors or advisory committees;Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees;Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees;Pfizer: Membership on an entity's Board of Directors or advisory committees;Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company;AstraZeneca: Membership on an entity's Board of Directors or advisory committees;Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees. Desai: Janssen R&D: Research Funding;Astex: Research Funding;Kura Oncology: Consultancy;Agios: Consultancy;Bristol Myers Squibb: Consultancy;Takeda: Consultancy. Goldberg: Celularity: Research Funding;Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees;Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees;Aptose: Consultancy, Research Funding;Prelude Therapeutics: Research Funding;DAVA Oncology: Honoraria;Pfizer: Research Funding;Arog: Research Funding;Aprea: Research Funding;AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Neuberg: Madrigal Pharmaceuticals: Other: Stock ownership;Pharmacyclics: Research Funding. Radhakrishnan: Janssen India: Honoraria;Dr Reddy's Laboratories: Honoraria, Membership on an entity's Board of Directors or advisory committees;Aurigene: Speakers Bureau;Novartis: Honoraria;Johnson and Johnson: Honoraria;Pfizer: Consultancy, Honoraria;Astrazeneca: Consultancy, Honoraria;Emcure Pharmaceuticals: Other: payment to institute;Cipla Pharmaceuticals: Honoraria, Other: payment to institute;Bristol Myers Squibb: Other: payment to institute;Roche: Honoraria, Other: payment to institute;Intas Pharmaceutical: Other: payment to institute;NATCO Pharmaceuticals: Research Funding. Sehn: Genmab: Consultancy;Debiopharm: Consultancy;Novartis: Consultancy. Sekeres: Novartis: Membership on an entity's Board of Directors or advisory committees;Takeda/Millenium: Membership on an entity's Board of Directors or advisory committees;BMS: Membership on an entity's Board of Directors or advisory committees. Tallman: Kura: Membership on an entity's Board of Directors or advisory committees;Syros: Membership on an entity's Board of Directors or advisory committees;Innate Pharma: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;Biosight: Membership on an entity's Board of Directors or advisory committees;Roche: Membership on an entity's Board of Directors or advisory committees;Jazz Pharma: Membership on an entity's Board of Directors or advisory committees;Oncolyze: Membership on an entity's Board of Directors or advisory committees;KAHR: Membership on an entity's Board of Directors or advisory committees;Orsenix: Membership on an entity's Board of Directors or advisory committees;Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees;Abbvie: Membership on an entity's Board of Directors or advisory committees;Amgen: Research Funding;Rafael Pharmaceuticals: Research Funding;Glycomimetics: Research Funding;Biosight: Research Funding;Orsenix: Research Funding;Abbvie: Research Funding;NYU Grand Rounds: Honoraria;Mayo Clinic: Honoraria;UC DAVIS: Honoraria;Northwell Grand Rounds: Honoraria;NYU Grand Rounds: Honoraria;Danbury Hospital Tumor Board: Honoraria;Acute Leukemia Forum: Honoraria;Miami Leukemia Symposium: Honoraria;New Orleans Cancer Symposium: Honoraria;ASH: Honoraria;NCCN: Honoraria.
ABSTRACT
Background: Predictors of severe infection and outcomes with COVID-19 in patients (pts) with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and myelodysplastic syndromes (MDS) are lacking. Pts with active disease may experience worse outcomes due to overall prognosis and cytopenias. Here we identify risk factors for severe COVID-19 infection and mortality in pts with AML, MDS, and ALL using the ASH RC COVID-19 Registry for Hematology. Methods: The ASH RC COVID-19 Registry for Hematology includes features and outcomes of a laboratory-confirmed or presumptive diagnosis of SARS-CoV-2 infection in adult pts with ongoing or a history of blood disorders. The Registry opened for data collection on April 1, 2020 and is a global effort housed on a secure data platform hosted by Prometheus Research, an IQVIA company. Data are made publicly available and regularly updated on the ASH RC website. Pt characteristics, outcomes, and predictors were analyzed and stratified by disease status (active initial diagnosis and relapsed/refractory vs. remission) and type of hematologic malignancy. Variables included age, comorbidities, type of hematologic malignancy (AML, MDS, ALL), neutrophil and lymphocyte count at time of COVID-19 diagnosis, and active treatment at the time of COVID-19 diagnosis. COVID-19 severity was defined as mild (no hospitalization required), moderate (hospitalization required), or severe (ICU admission required). Categorical pt characteristics for each response group and associations between response groups and characteristics (i.e., alive vs. dead, severity vs. non-severity) were summarized by frequency with differences between response groups evaluated by Fisher's exact test and odds ratios with 95% confidence intervals (CIs) estimated by logistic regression. Multivariable analyses identified independent predictors of outcomes. Results: Analyses were conducted on data from 257 pts with AML (n=135), MDS (n=40), and ALL (n=82);46% were in remission and 44% had active disease (10% unknown). Overall mortality from COVID-19 infection was 21%. Pts with active disease were significantly more likely to present with moderate and severe COVID-19 compared to those in remission (remission vs. active disease, severe 33% (n=20) vs. 67%(n=40), moderate 45% (n=35) vs.55% (n=42), and mild: 67% (n=56) vs. 33% (n=28), p value <0.001) (Figure 1). This was significant when categorized as severe vs. non severe as well (p=0.002). COVID-19 severity was also associated with AML diagnosis, major comorbidities, and neutropenia and lymphopenia at the time of COVID-19 diagnosis. Univariate analyses of increased mortality after COVID-19 diagnosis were significantly associated with advanced age, male sex, pre-diagnosis survival < 6 months, active disease status, neutropenia, lymphopenia and forgoing ICU care. Multivariable analyses in all pts (Figure 1), revealed that increased COVID-19 related mortality was significantly associated with neutropenia at diagnosis (OR 3.15, 95% C.I. 1.31-8.08, p=0.01), estimated pre-COVID-19 prognosis of < 6 months (OR 8.58, 95% C.I. 3.24-24.46, p<0.001) and forgoing ICU care (OR 6.66, 95% C.I. 2.56-18.23, p<0.001). Among hospitalized pts, increased COVID-19 mortality was associated with estimated pre-COVID-19 prognosis of < 6 months (OR 6.77, 95% C.I. 2.34-22.24, p<0.001) and forgoing ICU care (OR 3.98, 95% C.I. 1.45-11.66, p=0.007). Pts who were older, male, smokers, with active disease, or estimated to have pre-COVID-19 survival of < 6 months were more likely to forgo ICU care. Forgoing ICU care (n=37,16%) was associated with a higher COVID-19 mortality in all pts (n=234, OR 15.6, 95% C.I. 6.4-40.9, p<0.001), hospitalized pts (n=143, OR 9.2, 95% C.I., 3.5-26.5, p<0.001) and in pts where ICU admission was indicated and declined (n=61 OR 5.6, 95% C.I. 1.1-56.4, p=0.03)). Neither active disease status nor ongoing cancer treatment were associated with increased mortality among hospitalized patients. Conclusions: These data suggest that patients with active disease experience significantly higher COVID-19 severity but not increased mortality from COVID-19. Patients who had neutropenia and a pre-COVID-19 prognosis of < 6 months had higher mortality from COVID-19 infection and may be more likely to forgo ICU care. If desired by patients, aggressive support for hospitalized patients with COVID-19 is appropriate regardless of remission status. [Formula presented] Disclosures: Desai: Agios: Consultancy;Janssen R&D: Research Funding;Kura Oncology: Consultancy;Bristol Myers Squibb: Consultancy;Astex: Research Funding;Takeda: Consultancy. Goldberg: AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Aprea: Research Funding;Prelude Therapeutics: Research Funding;Pfizer: Research Funding;Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees;DAVA Oncology: Honoraria;Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees;Arog: Research Funding;Celularity: Research Funding;Aptose: Consultancy, Research Funding. Anderson: Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees;Celgene: Membership on an entity's Board of Directors or advisory committees;Gilead: Membership on an entity's Board of Directors or advisory committees;Janssen: Membership on an entity's Board of Directors or advisory committees;Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees;Pfizer: Membership on an entity's Board of Directors or advisory committees;Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees;Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company;AstraZeneca: Membership on an entity's Board of Directors or advisory committees;Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees. Neuberg: Pharmacyclics: Research Funding;Madrigal Pharmaceuticals: Other: Stock ownership. Radhakrishnan: Emcure Pharmaceuticals: Other: payment to institute;Bristol Myers Squibb: Other: payment to institute;Astrazeneca: Consultancy, Honoraria;Cipla Pharmaceuticals: Honoraria, Other: payment to institute;Pfizer: Consultancy, Honoraria;Johnson and Johnson: Honoraria;Novartis: Honoraria;Aurigene: Speakers Bureau;Roche: Honoraria, Other: payment to institute;Intas Pharmaceutical: Other: payment to institute;Dr Reddy's Laboratories: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen India: Honoraria;NATCO Pharmaceuticals: Research Funding. Roboz: Novartis: Consultancy;Mesoblast: Consultancy;Amgen: Consultancy;Actinium: Consultancy;AbbVie: Consultancy;Janssen: Consultancy;Blueprint Medicines: Consultancy;Astex: Consultancy;Janssen: Research Funding;Daiichi Sankyo: Consultancy;Jazz: Consultancy;Agios: Consultancy;Glaxo SmithKline: Consultancy;Celgene: Consultancy;Otsuka: Consultancy;Astellas: Consultancy;Helsinn: Consultancy;MEI Pharma - IDMC Chair: Consultancy;Jasper Therapeutics: Consultancy;Bristol Myers Squibb: Consultancy;AstraZeneca: Consultancy;Bayer: Consultancy;Pfizer: Consultancy;Roche/Genentech: Consultancy. Sehn: Novartis: Consultancy;Genmab: Consultancy;Debiopharm: Consultancy. Sekeres: Takeda/Millenium: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;BMS: Membership on an entity's Board of Directors or advisory committees. Tallman: Syros: Membership on an entity's Board of Directors or advisory committees;Kura: Membership on an entity's Board of Directors or advisory committees;NYU Grand Rounds: Honoraria;Innate Pharma: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;Biosight: Membership on an entity's Board of Directors or advisory committees;Roche: Membership on an entity's Board of Directors or advisory committees;Jazz Pharma: Membership on an entity's Board of Directors or advisory committees;Oncolyze: Membership on an entity's Board of Directors or advisory committees;KAHR: Membership on an entity's Board of Directors or advisory committees;Orsenix: Membership on an entity's Board of Directors or advisory committees;Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees;Abbvie: Membership on an entity's Board of Directors or advisory committees;Amgen: Research Funding;Rafael Pharmaceuticals: Research Funding;Glycomimetics: Research Funding;Biosight: Research Funding;Orsenix: Research Funding;Abbvie: Research Funding;Mayo Clinic: Honoraria;UC DAVIS: Honoraria;Northwell Grand Rounds: Honoraria;NYU Grand Rounds: Honoraria;Danbury Hospital Tumor Board: Honoraria;Acute Leukemia Forum: Honoraria;Miami Leukemia Symposium: Honoraria;New Orleans Cancer Symposium: Honoraria;ASH: Honoraria;NCCN: Honoraria. Wood: Pfizer: Research Funding;Teladoc: Consultancy;Koneksa Health: Consultancy, Current equity holder in publicly-traded company.
ABSTRACT
Introduction: The NHLBI MDS Natural History Study (NCT02775383) is an ongoing prospective cohort study conducted across 144 sites in the U.S. and Israel intended to establish a data and biospecimen repository to advance the understanding of MDS. In response to the COVID-19 pandemic, the study also collected data on COVID-19 infection and management. Here, we report a summary of COVID-19 outcomes from participants in this study and the impact of the pandemic on study operations. Methods: This prospective cohort study initiated in June, 2016 is enrolling patients (pts) undergoing diagnostic work up for suspected or newly diagnosed MDS or MDS/myeloproliferative neoplasms (MPNs) in the setting of cytopenia. Study enrollment was paused from Mar. 27, 2020 to May 18, 2020 due to COVID-19. Previously untreated pts underwent a bone marrow assessment with a centralized histopathology review at enrollment for assignment to a longitudinal cohort (MDS, MDS/MPN overlap, idiopathic cytopenia of undetermined significance (ICUS), acute myeloid leukemia (AML) with <30% blasts, or “At-Risk” (pts with sub-threshold dysplasia, select karyotype, or select genetic mutations) for follow-up every six months;or a cross-sectional cohort (other cytopenia or cancers) with no further follow-up. COVID-19 outcomes, including tests, status, hospitalizations and treatments for COVID-19, were collected for all eligible pts. Protocol deviations related to COVID-19 were also collected. Fisher's exact test was used for comparing the proportions of pts tested or positive between groups. Results: Of 758 eligible pts with available COVID-19 data, 507 (67%) were assigned to the longitudinal cohort and 251 (33%) to the cross-sectional cohort or are pending assignment. Among longitudinal pts, 74 (15%) had ICUS, 240 (47%) MDS, 47 (9%) MDS/MPN overlap, 11 (2%) AML with <30% blasts, and 135 (27%) At-Risk for MDS. The median age over all pts was 72 years (range=21-95) and 66% were male, 92% White, 4% Black, 2% Asian, and 2% other. Among 244 pts (32%) tested for COVID-19 (Table 1), 23 (9%) were positive. Twelve (>50% of the positive pts) were in Wisconsin, California (CA), and Missouri (Figure 1), with 8 identified from Sep. to Dec. 2020, which overlaps with third waves of COVID-19 reported in CA and in the Midwest. Tests from 17 (74%) of the 23 pts were based on a polymerase chain reaction (PCR) assay. The proportion of pts positive were similar between pooled disease (ICUS, MDS, MDS/MPN, AML <30%), At-Risk, and cross-sectional groups (8%, 8%, 16%, respectively;Table 2) but the proportions tested differed significantly (39%, 28%, and 25%, respectively, p=0.004). Among all positive pts, 21 (91%) are recovering or have recovered (16 with sequelae), 1 (4%) died, and 1 outcome is unknown (Table 1). The one participant who died had MDS with excess blasts-1 (MDS-EB1, 5-9% blasts). Eight pts (35% of positive pts) required hospitalization (median duration of 7 days (range=2-17)) or treatment (tx) in response to COVID-19, 7 of whom required both. In the 8 pts who required tx for COVID-19, 4 reported Remdesivir-use, 3 of whom were diagnosed with MDS or MDS/MPN overlap. The study monthly accrual rates were similar when compared pre- vs. post-study pause (23 vs. 22 pts, respectively) but the rate of missed follow-up visits increased from 5% to 11% post-pause. About half (49%) of the 144 COVID-19-related study deviations occurred during the months the study was paused. Conclusions: In this analysis of 758 pts with MDS and related conditions, the largest reported for these diagnoses, the COVID-19 mortality rate (13%) in MDS was lower than has been reported in a smaller (n=61) case study (39%, Feld et al Blood 2020) but is similar to the rates for MDS observed annually each year prior to study pause (range=11-19%) and to the rate reported in a larger (n=2186) observational study of cancer patients (16%, Rivera et al Cancer Discov 2020). Infection rates were similar across disease groups. The pandemic also resulted in substantial study-specific challenges, including incre sed rate of deviations, the study being paused, and difficulty sourcing material for biospecimen processing. Data on vaccine efficacy and rates of pts with long-haul symptoms post-COVID may be of interest in future work. [Formula presented] Disclosures: Padron: BMS: Research Funding;Kura: Research Funding;Taiho: Honoraria;Stemline: Honoraria;Blueprint: Honoraria;Incyte: Research Funding. Komrokji: Novartis: Honoraria;Geron: Honoraria;Acceleron: Honoraria;Agios: Honoraria, Speakers Bureau;Abbvie: Honoraria, Speakers Bureau;JAZZ: Honoraria, Speakers Bureau;BMS: Honoraria, Speakers Bureau. Saber: Govt. COI: Other. Al Baghdadi: Bristol-Myers Squibb: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees;AstraZeneca: Current holder of individual stocks in a privately-held company;Epizyme: Current holder of individual stocks in a privately-held company;Heron Therapeutics: Current holder of individual stocks in a privately-held company;Morphosys: Membership on an entity's Board of Directors or advisory committees;Karyopharm: Membership on an entity's Board of Directors or advisory committees;Cardinal Health: Membership on an entity's Board of Directors or advisory committees. DeZern: Taiho: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees;Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees;Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sekeres: Novartis: Membership on an entity's Board of Directors or advisory committees;Takeda/Millenium: Membership on an entity's Board of Directors or advisory committees;BMS: Membership on an entity's Board of Directors or advisory committees.
ABSTRACT
Background: Isocitrate dehydrogenase 2 (IDH2) mutations occur in 5% of patients (pts) with MDS. Enasidenib (ENA) is a selective oral inhibitor of the mutant IDH2 enzyme with single-agent activity in relapsed/refractory acute myeloid leukemia (AML). We report the results of the open label phase II study designed to evaluate the efficacy and tolerability of ENA, as monotherapy or in combination with azacitidine (AZA) in pts with higher-risk IDH2-mutated MDS (NCT03383575). Methods: Pts with higher-risk [Revised International Prognostic Scoring System risk > 3 or high molecular risk (HMR)] MDS/CMML or LB AML naïve to hypomethylating agents (HMA) received ENA100 mg orally daily for 28 d of each 28-d cycle + AZA 75 mg/m2 IV or SC on d 1-7 of each cycle (ENA+AZA), and pts with refractory or progressive MDS to prior HMA therapy received ENA alone (ENA), in 28-d cycles until unacceptable toxicity, relapse, transformation to AML, or progression. The primary endpoint was overall response rate (ORR) [complete remission (CR), marrow CR (mCR), partial remission (PR) and hematologic improvement (HI)]. Other endpoints include safety, and survival outcomes. Results: 48 pts received ENA+AZA (n = 26) or ENA (n = 22). The median age was 73 yrs (range, 46-83). Most pts (72%) had HMR: ASXL1 (39%), and RUNX1 (17%). Median number Tx cycles was 4 (2-32) in the ENA+AZA, and 7 (1-23) in the ENA arm. Common Tx-related grade 3-4 AEs in the ENA+AZA arm were neutropenia (64%), thrombocytopenia (28%), and anemia (8%);these occurred in 10%, 0%, and 5%, in the ENA arm. Grade 3-4 infections occurred in 32% (ENA+AZA) and 14% (ENA). IDH differentiation syndrome occurred in 3 pts (12%) in the ENA+AZA and 5 pts (24%) in the ENA arm. Two deaths occurred during the initial 60 d, both unrelated to study and due to COVID. In response-evaluable pts (n=46), ORR was 84% (n = 21/25;24% CR + 8% PR+44% mCR+ 8% HI] in the treatment naïve ENA+AZA and 43% (n = 9/21;24% CR+5%PR+5% mCR+10% HI) in the HMA failure ENA arm (Table). Most common reason for Tx discontinuation was disease progression (ENA+AZA 20%, ENA 33%).5 pts (20%) received HCT in the ENA+AZA and 1 (5%) in the ENA arm. 7 pts in the ENA+AZA and 5 in the ENA arm were ongoing at data cutoff (Dec 31, 2020). After a median follow up of 12.6 mo, median OS was 32.2 mo in the ENA+AZA and 21.3 mo in the ENA arm. Conclusions: ENA is well tolerated and shows promising efficacy in IDH2-mutated higher risk MDS. Follow up and accrual is ongoing to better define duration and biomarkers of response.