Patterns of lower risk myelodysplastic syndrome progression: factors predicting progression to high-risk myelodysplastic syndrome and acute myeloid leukemia

The patterns of low risk myelodysplastic syndrome (MDS) progression, and the clinical and molecular features of those patterns are not well described. We divided our low risk (LR) MDS patients (n=1914) into 4 cohorts: 1) Patients who remained LR-MDS (LR-LR; n=1300; 68%), 2) Patients who progressed from LR to HR MDS (LR-HR) without AML transformation (n=317; 16.5%), 3) Patients who progressed from LR to HR MDS and then AML (LR-HR-AML; n=124; 6.5%), 4) Patients who progressed from LR MDS to AML directly (LR-AML; n=173; 9%). Risk factors for progression included male gender, low absolute neutrophil count (ANC), low platelet count, high bone marrow (BM) blasts, ferritin >1000 mcg/L, albumi

AML-225: Outcome with Intensive Chemotherapy vs Hypomethylating Agent-Based Induction Strategies in Patients Older Than 70 Years with Newly Diagnosed, Favorable-Risk Acute Myeloid Leukemia

Real-world evidence is lacking regarding the effectiveness of intensive and non-intensive induction strategies in elderly patients with favorable-risk acute myeloid leukemia (AML). To estimate the rates of complete remission (CR), CR+ CR with incomplete count recovery (CRi), and overall survival (OS) in patients receiving intensive chemotherapy (IC) and hypomethylating agent (HMA)-based induction regimens. In this retrospective study, clinical and genomic data were collected by review of records of eligible patients treated at Moffitt Cancer Center. Statistical analyses were performed using SPSS. Elderly (age > 70 years) patients with newly diagnosed, favorable-risk (ELN 2017) AML. CR, CR+ CRi, OS. Out of total 53 patients, 36 (68%) received IC, and 17 (32%) received HMA-based induction regimen. Median age at diagnosis was 74 years (range 70–85). Core binding factor (CBF) abnormalities were detected in 47% patients; 28% had secondary AML. Median blast count was significantly higher in patients receiving IC vs HMA (58% vs 32%, p=0.01). Predominant induction regimen was “7+3” (86%) in the IC group and azacytidine alone (n=11) in HMA cohort. Rate of composite CR (CR+ CRi) was significantly better at 69% (50% CR) in the IC group, compared to 35% (24% CR) with HMA (p=0.01). Six patients on IC and 1 on HMA had early (<30 d) induction-related mortality. Both groups had comparable relapse rates (overall 34%). Median OS was 24.7 months in IC vs 17.5 months in the HMA group, trending toward statistical significance (p=0.058). Overall, 23% patients in the IC group were alive at 5 years, compared to 7% with HMA. In patients with CBF-AML (n=25), median OS was not reached for IC vs 23 months with HMA (p= 0.076); CBF-AML was an independent predictor of survival in the study population. Six patients (3 post-relapse) from the IC group underwent allogeneic stem cell transplant. Elderly favorable-risk AML patients had a significantly better composite CR rate on induction treatment with IC than with HMA, with a trend toward improved OS with IC-based induction. A multicenter study with a larger sample size is ongoing to address this question further

Outcome with Intensive Chemotherapy Compared to Hypomethylating Agent- Based Induction in Patients Aged 70 Years or Older with Newly Diagnosed Favorable Risk Acute Myeloid Leukemia

Abstract Introduction: Elderly fit patients (pts) with favorable risk (ELN 2017) acute myeloid leukemia (FR-AML) are traditionally treated with intensive chemotherapy (IC-most commonly 7+3) as induction treatment, based on data extrapolated from studies in pts 65 yrs) reported improved outcome (1-yr survival rate- 80%) with the combination of hypomethylating agent and venetoclax (HMA-Ven) compared to HMA alone. However, real world evidence continues to lack on efficacy and long-term outcome of intensive and non-intensive induction strategies in very elderly pts (≥70 yrs) with FR-AML, including core-binding factor (CBF)-AML. Methods: In this multicenter retrospective study, clinical, demographic, and genomic data were collected by review of records of pts aged ≥70 yrs with FR-AML (ELN 2017), treated at Moffitt Cancer Center, University of Colorado, Yale Cancer Center, and University of Miami. Patients who received IC, HMA-Ven, or HMA alone as induction treatment were included in the final analyses. Survival estimates using Kaplan-Meier statistics and multivariate analysis with Cox regression were performed in SPSS (v.26). Results: Out of 101 pts included in our study, 45 (45%) received IC, whereas induction regimens were HMA-Ven in 32 (32%) and HMA alone in 24 (24%) pts [Table 1]. Median age at diagnosis was 74 yrs (range 70-92); pts receiving HMA or HMA-Ven were older (p=0.005) than those on IC. Majority of pts were white (90%), and gender was distributed equally. A performance status (PS) of ECOG ≥2 was noted in 18% pts. Abnormalities in CBF were detected in 29% of pts overall (more commonly in IC group), and 26% had secondary AML. Median bone marrow blast counts were comparable across three groups. No significant difference was observed among groups in frequencies of NPM1, CEBPA, IDH1, IDH2, and FLT3-ITD mutations. Median duration of follow up was 31.7 months (mo). Among evaluable pts (n=95), the composite complete remission [cCR- CR + CR with incomplete count recovery (CRi)] rate was significantly better in pts on HMA-Ven, compared to IC (97% vs. 66%, p= 0.002) or HMA alone [Table 2]. CR was noted in 20 (69%) pts receiving HMA-Ven vs. 22 (50%) with IC- based induction (p= 0.237). Overall, 10 (10%) pts died within 30 days of induction, with a trend for higher 30-day and 60-day mortality (18%) with IC (p=0.059). In our study, 34% pts relapsed, with similar early (12 mo) relapse rates across groups. In pts achieving a CR or CRi, median relapse free survival was 7.93 mo, with no significant difference between cohorts. Total 9 pts (IC-8, HMA-Ven-1), including 3 with relapsed AML, underwent allogeneic stem cell transplant (allo-SCT). Median overall survival (mOS) was 25.5 mo in pts with CBF-AML (n=29) and 16.5 mo in NPM1-mutant (n= 67) cohort. Patients on IC had significantly improved mOS than those on HMA alone (24.7 vs. 14.3 mo, p= 0.008, Figure 1); however, it was not an independent predictor in multivariate analysis after adjusting for age, PS, and allo-SCT. No significant mOS difference was observed between pts treated with IC and HMA-Ven as induction regimen (24.7 vs. 19.6 mo, p= 0.836). Estimated 5-yr survival rate was 30% with HMA-Ven, 22% with IC, and 4% with HMA. In pts with NPM1-mutant AML, mOS was not significantly different between IC and HMA-Ven groups (16.6 mo vs. 29.2 mo, p= 0.364). In CBF-AML, mOS was not reached in pts on IC vs. 7.27 mo in HMA-Ven group (p= 0.076). Conclusions: Induction treatment with HMA-Ven led to a significantly high cCR rate (97%) in elderly (≥ 70 yrs) pts with FR-AML. There was no significant difference in mOS in pts treated with IC and HMA-Ven, both overall and in NPM1-mutant cohort. Among pts with CBF-AML, mOS was not reached in IC group, with a 5-year survival rate of 47%, although small sample size in the HMA-Ven group limits inference from this comparison. NPM-1 mutant elderly FR-AML pts can be treated with HMA-Ven regimen, whereas elderly pts with CBF-AML should be treated with IC if fit, until further data with HMA-Ven combination is available. Figure 1 Figure 1. Disclosures Sallman: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Aprea: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Magenta: Consultancy; Kite: Membership on an entity's Board of Directors or advisory committees; Syndax: Membership on an entity's Board of Directors or advisory committees; Intellia: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Shattuck Labs: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; Incyte: Speakers Bureau. Padron: Stemline: Honoraria; BMS: Research Funding; Incyte: Research Funding; Taiho: Honoraria; Kura: Research Funding; Blueprint: Honoraria. Sweet: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; AROG: Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Bristol Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lancet: AbbVie: Consultancy; BerGenBio: Consultancy; Agios: Consultancy; Celgene/BMS: Consultancy; Daiichi Sankyo: Consultancy; Astellas: Consultancy; Jazz: Consultancy; ElevateBio Management: Consultancy; Millenium Pharma/Takeda: Consultancy. Watts: Takeda: Consultancy, Research Funding; Genentech: Consultancy; Rafael Pharma: Consultancy; Celgene/BMS: Consultancy. Pollyea: AbbVie: Consultancy, Research Funding; Syndax: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Genentech: Consultancy; Karyopharm: Consultancy; Novartis: Consultancy; Daiichi Sankyo: Consultancy; Celgene/BMS: Consultancy; Pfizer: Consultancy; Takeda: Consultancy; Agios: Consultancy; Glycomimetics: Other. Zeidan: Genentech: Consultancy; Daiichi Sankyo: Consultancy; Kura: Consultancy, Other: Clinical Trial Committees; Novartis: Consultancy, Other: Clinical Trial Committees, Travel support, Research Funding; Jazz: Consultancy; Amgen: Consultancy, Research Funding; Loxo Oncology: Consultancy, Other: Clinical Trial Committees; Pfizer: Other: Travel support, Research Funding; Geron: Other: Clinical Trial Committees; Cardiff Oncology: Consultancy, Other: Travel support, Research Funding; Agios: Consultancy; Epizyme: Consultancy; Jasper: Consultancy; BioCryst: Other: Clinical Trial Committees; Janssen: Consultancy; AstraZeneca: Consultancy; Aprea: Consultancy, Research Funding; BeyondSpring: Consultancy; Boehringer Ingelheim: Consultancy, Research Funding; Astex: Research Funding; Astellas: Consultancy; Ionis: Consultancy; Incyte: Consultancy, Research Funding; Gilead: Consultancy, Other: Clinical Trial Committees; BMS: Consultancy, Other: Clinical Trial Committees, Research Funding; Acceleron: Consultancy, Research Funding; ADC Therapeutics: Research Funding; AbbVie: Consultancy, Other: Clinical Trial Committees, Research Funding. Komrokji: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Acceleron: Consultancy; Taiho Oncology: Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Speakers Bureau; Geron: Consultancy; PharmaEssentia: Membership on an entity's Board of Directors or advisory committees; BMSCelgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy