ALBERT

Description: Introduction Early bone marrow (BM) evaluation (during aplasia or at “day 14” (D14)) in patients with AML undergoing conventional induction therapy has been adopted from clinical practice in pediatric acute lymphoblastic leukemia (ALL). While it has been shown that early persistence of AML correlates with decreased complete remission (CR) rates and overall survival (OS), unlike in ALL, there are no data to indicate that early initiation of re-induction therapy based on these findings will positively influence outcome. In fact, early re-induction, especially in older patients, may increase morbidity and mortality from prolonged cytopenias, infectious complications, and longer hospital stays. Moreover, it can be challenging to determine the nature of scattered blasts identified in a hypocellular BM at D14, as they may represent normal recovering marrow elements or malignant blasts. Even if malignant, the chemosensitivityof these cells will only be fully determined by later assessment of the BM at the time of expected count recovery (“day 28”). For these reasons, early re-induction therapy may not be advisable. In this retrospective study, we sought to evaluate the validity of D14 BM assessments as post-therapy prognostication to guide treatment decisions in AML. Methods We conducted a retrospective institutional study (2006-2014) of AML patients undergoing routine induction chemotherapy where diagnostic, interim (around D14) and recovery (D21-42) BM evaluations were available for review. Clinical information and pathology data were retrieved from our institutional database. Responses at D14 were categorized morphologically into three categories: optimal response (OR, blasts ≤5%), indeterminate response (IR, blasts 6-19%), and residual leukemia (RL, blasts ≥20% or a relative decrease in blast count from baseline of

Description: Background There is ample data for the response rates and clinical outcomes for patients with newly diagnosed multiple myeloma (MM) treated with first-line lenalidomide and dexamethasone (LEN/DEX). Phase II and III studies have reported objective response rates (ORR) in the range of 70-90%.  However, extrapolating from clinical trials to ‘real world' clinical practice is sometimes difficult. This is particularly so when it comes to large city hospital systems such as Jackson Memorial Hospital (JMH) in Miami, Florida. JMH is the third-largest public hospital and third-largest teaching hospital in the United States. Patients are primarily uninsured or insured through Medicaid. Additionally, one might surmise, that for a medication like LEN- with a relatively narrow therapeutic index, high cost, and cumbersome prescribing/dispensing requirements- outcomes in the ‘real world' might be inferior to those cited in clinical study. We endeavored to explore such outcomes in JMH to determine whether the benefits of this high cost drug in this setting are concordant with published data. Methods We conducted a retrospective analysis of all patients enrolled into the Celgene patient assistance program and prescribed LEN from January 1, 2010 through July 30, 2013 at JMH. We identified 96 patients enrolled into this program, 35 patients received LEN/DEX as first-line therapy for MM and are evaluable for this analysis. The primary end-point for analysis was response at 4 months. Results Medical records of 35 patients were reviewed. The mean age was 59 (46-75), majority of patients were female (60%), and 29% were black. Consistent with our patient population, 71.4% of patients were Hispanic, 44% were uninsured, and 64% had Medicaid. IgG (60%) was the most common heavy chain involved while 3 patients had light chain disease only. The majority of patients (88.6%) had stage III disease by the Durie-Salmon criteria, and 37.1% had ISS stage III disease. Cytogenetic studies were evaluable in 30 patients: 66.7% were standard-risk, 30% intermediate-risk and 3.3 % high-risk according to mSMART risk classification. At 4-month follow-up, 26 (74.3%) patients had an OR: 6 (17.1%) patients had CR, 7 (20%) had VGPR, and 13 (37.1%) had PR. 6 (17.1%) patients had progressive disease, change in therapy, or were lost to follow-up. There were no documented deep venous thromboses, a known risk of LEN therapy. Only 8 patients (23%) underwent autologous stem cell transplant following primary therapy. Conclusion Responses with upfront LEN/DEX in MM at JMH, were relatively similar to published data in large clinical studies. This provides support for the extrapolation of data from well supported clinical trials at fully-resourced medical institutions, for an oral chemotherapy drug with significant potential toxicities and logistical barriers, to a primarily Medicaid patient population in a county hospital. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction: Current therapy for acute myeloid leukemia (AML) is inadequate. Treatment of older patients considered unfit for standard induction therapy is particularly challenging (Juliusson et al. Blood 2009). Hypomethylating agents (HMA) are commonly used alternatives for these patients (Fenaux et al. JCO 2010). In the case of azacitidine, complete and partial response rates range between 15-30% (Maurillo et al. Cancer 2012) and the addition of other drugs (e.g. lenalidomide and vorinostat) has been limited by toxicity. In this study, we sought to improve the activity of azacitidine by adding the non-steroidal anti-inflammatory drug (NSAID), sodium salicylate (NSal). NSAIDs exert anti-cancer effects through impaired signal transduction (inhibition of NF-kB and Wnt/B catenin pathways) (Kop et al. Science 1994; Reya et al. Nature 2003), epigenetic modulation and disruption of cellular metabolism (activation of AMPK) (Wang et al. CMLS 2013). In addition, previous reports have demonstrated that NSal combines synergistically with established anti-leukemic agents (daunorubicin) (Klampfer et al. Blood 1999), through down-regulation of the anti-apoptotic protein Mcl-1. Importantly, NSal has no effect on platelet function and a small pilot trial (N=11) confirmed the clinical feasibility of this agent in patients with refractory myeloid neoplasms (Klimek et al. Leukemia Research 2012). In this study, therapeutic plasma concentrations of NSal were safely achieved without excessive NSAID class effects (GI and renal toxicity, bleeding). Here, we report the in vitro effects of NSal combined with azacitidine and suggest a rationale for exploring this combination further in the clinic. Methods: AML cell lines (HL-60, KG-1a and THP-1) were treated with increasing concentrations of NSal (0.2–20mM), azacitidine (0.02-10µM) and both agents combined. Consequent effects on cell viability were measured by trypan blue exclusion and cell proliferation assay (MTT based). Apoptosis was measured by FACS analysis for propidium iodide (PI) and annexin V binding. Synergistic lethality was calculated using the Chou-Talalay method (Calcusyn software). Critical mediators underlying mechanism were measured by immunoblotting (Mcl-1). Results: The degree of apoptosis in AML cells treated with sub-lethal concentrations of NSal (0.2-20mM) and azacitidine (0.02-10µM) was compared to the degree of apoptosis induced by the combination. Little effect on the viability of HL-60, KG-1a and THP-1 cell lines was observed after 48 hours exposure to either agent alone, however, in the presence of 2 µM azacitidine and 2mM NSal, 39.2% of THP-1 cells were dead at 48 hours (annexin V binding). The combination of 0.2 µM azacitidine and 2mM NSal had significantly inhibited cell proliferation at 72 hours. Cell proliferation decreased by 47.4%, 25%, and 66.1% in HL-60, KG-1a, and THP-1, cell lines, respectively. Combination index (CI) values (Calcusyn software) were less than 1 indicating synergistic activity. The expression of Mcl-1 decreased in a dose- and time-dependent manner in salicylate treated cells which might account for its ability to enhance cell killing by azacitidine. Conclusions: Sodium salicylate has a priming effect when combined with azacitidine in pre-clinical models of AML. Despite the high pre-clinical concentrations of NSal evaluated, previous studies have confirmed the feasibility of achieving therapeutically active plasma concentrations in patients (Klimek et al. Leukemia Research 2012). This study forms a rationale for a clinical investigation of this approach. Additional in vitro mechanistic studies elucidating the combined effects of NSal and azacitidine will be presented. Disclosures No relevant conflicts of interest to declare.

Description: Introduction The identification of somatic genomic alterations in cancer has brought forth a paradigm change in the personalized management of patients with acute myeloid leukemia (AML). This is exemplified by the recent FDA approvals with the targeted small molecule inhibitors of mutant IDH1 (ivosidenib) and IDH2 (enasidenib) for patients with relapsed/refractory AML. IDH1/2 mutations have been reported to occur in approximately 16-20% of patients with AML based on the largest published cohorts to date (Dinardo et al., Am J Hematol, 2015; Papaemmanuil et al., NEJM, 2016). However, there remains a paucity of data on the frequency of IDH1/2 and other targetable mutations in extramedullary manifestations of AML (i.e. myeloid sarcoma and leukemia cutis; EM-AML). We sought to characterize the mutational landscape of EM-AML, with a focus on determining the frequency of IDH1/2 mutations. Methods This is a multi-institutional retrospective analysis of patients diagnosed with EM-AML, who were treated at Moffitt Cancer Center or Memorial Healthcare System and underwent next-generation sequencing (NGS). All patients were evaluated for IDH1/2 mutations and up to 435 additional genes. Clinical variables and outcomes of EM-AML patients were characterized at the time of sample procurement. Additionally, we acquired additional de-identified NGS data on EM-AML patients who underwent sequencing of the EM site at Genoptix. We describe the mutational landscape of patients and compared the frequency of IDH1/2 mutations to historical controls in AML from the published literature using Fisher's exact test. Kaplan-Meier curves were used to estimate overall survival (OS) and analyzed from the date of mutation identification. Results Thirty-five patients with EM-AML were identified (22 in the clinical cohort and 13 in the Genoptix cohort) and are included in this analysis. The distribution of EM-AML diagnoses were myeloid sarcoma in 71% of cases (n=25) and leukemia cutis in 29% (n=10). The sequenced samples were from an extramedullary site for 63% (n=22) of the cases. The median age of the cohort was 64 (IQR 52 - 72) with a male predominance (55%). Of the clinical cohort, 68% (n=15) were non-Hispanic White, 23% (n=5) were Hispanic, and 9% (n=2) were Black. The molecular landscape of the cohort is shown in Figure 1. The frequency of IDH1/2 mutations was 31% (11/35), with IDH1 and IDH2 mutations reported in 17% (n=6) and 14% (n=5) of cases, respectively. All IDH1 mutations were at position R132 (4 R132H and 2 R132C) and all IDH2 mutations were at R140 (4 R140Q and 1 R140G). The other most frequent genomic alterations were DNMT3A (29%), NPM1 (26%), FLT3 (23%; ITD in 18% and TKD in 5%; 11% in IDH wildtype), NRAS (21%), TET2 (17%), and ASXL1 (17%). Mutations in DNA methylation occurred in 54% of patients (n=19). Co-occurring NRAS/KRAS mutations were more frequent in IDH mutant patients (45%; 5/11) compared to 12% (3/24) of IDH wild type patients (P=0.01). DNMT3A mutations were reported in 45% (5/11) of IDH mutant cases compared to 21% (5/24) of IDH wildtype cases, although this was not statistically significant (P=0.23). In comparison to a historical frequency of IDH1/2 mutations in AML patients of 17.4% (n=2366), EM-AML patients had an increased frequency of 31% (P=0.04). The median OS of the cohort was 13.6 months. Within the clinical cohort 50% (4/8) of the IDH1/2 mutant patients were treated with an IDH inhibitor with CR in 1 patient, CRi in 1 patient, and stable disease in 2 patients. The patient who achieved CR developed widespread leukemia cutis during cycle 1 of enasidenib which resolved over 6 months and is in durable CR for 15 months. Conclusion Overall, EM-AML patients had targetable mutations (i.e. IDH1/IDH2/FLT3) in 40% of cases with an increased frequency of IDH1/2 mutations (31%) in comparison to the general AML population. IDH mutant EM-AML patients achieved clinical benefit to specific inhibitors. These data support mutational analysis of EM-AML patients in order to personalize therapeutic options for our patients. Figure 1. Figure 1. Disclosures Bhagat: Genoptix: Employment. Watts:Takeda: Research Funding; Jazz Pharma: Consultancy, Speakers Bureau. Sweet:Novartis: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Jazz: Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Jazz: Speakers Bureau; BMS: Honoraria; Astellas: Consultancy; Celgene: Honoraria, Speakers Bureau; Astellas: Consultancy; Agios: Consultancy; Agios: Consultancy; Phizer: Consultancy; Phizer: Consultancy; BMS: Honoraria. Komrokji:Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Sallman:Celgene: Research Funding, Speakers Bureau.

Description: Background: Approval of CPX-351 has changed the treatment landscape for therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) and has become the new standard-of-care. Response rates (RR) (complete remission (CR) and CR with incomplete count recovery (CRi)) with CPX-351 in the phase 3 clinical trial were 47.7%, however, comprehensive molecular characterization to investigate impact on response was lacking. Herein, we annotated the molecular profiles of patients (pts) treated with CPX-351 to identify outcome interaction with specific somatic mutations. Methods: We retrospectively analyzed a combined cohort of 111 pts treated with CPX-351 from Moffitt Cancer Center, Weill Cornell Medical College, and Memorial Sloan Kettering Cancer Center. A total 85 pts that had next-generation sequencing (NGS) prior to treatment were included in the analysis. Those genes analyzed with 〉5% mutation frequency are summarized in Figure 1A. Demographics, disease-specific variables, and overall outcomes were analyzed and responders (RES) were defined as pts achieving CR/CRi after 1-2 cycles of CPX-351 compared to nonresponders (NR). AML patients with diagnosis of antecedent myeloid malignancy are defined as sAML. Pts receiving a second cycle of induction (reinduction) with a different regimen were considered to be NR to CPX-351. We utilized Fisher's exact test to determine two-tailed significance with p-value

Description: Background: Older patients with acute myeloid leukemia (AML) have inferior outcomes when compared to younger patients. Hypomethylating agents (HMA) were established as the standard of care for patients who are unfit for intensive induction chemotherapy until HMA and venetoclax (HMA+ven) combination approval by the FDA in December 2018. Approval of HMA+ven was based on an early phase study which produced high response rates; however, the combination was not compared head-to-head with HMA alone. A randomized phase 3 study is currently underway. There is no data available comparing HMA+ven to HMA monotherapy in older patients (age ≥70 years), thus we aimed to characterize responses in older patients when treated with these two regimens. Methods: We retrospectively reviewed clinical and molecular data on 225 patients at Moffitt Cancer Center and Memorial Health System with newly diagnosed AML who were ≥ 70 years old and were treated with HMA monotherapy or HMA+ven combination. Clinical data was abstracted in accordance with institutional review board approved protocol. Patients were then divided in two subgroups: Cohort A) HMA monotherapy and B) HMA+ven combination. We calculated overall response rates (ORR) defined as patients achieving complete remission (CR), CR with incomplete hematologic recovery (CRi) or morphologic leukemia free state (MLFS). Fisher's Exact method was utilized to determine significance for categorical variables. All reported p-values are two sided. Next generation sequencing (NGS) results were analyzed using the TruSight Myeloid-54 gene panel with a sensitivity of 5%, and were characterized in patients treated in cohort B. Results: Among the 225 patients, 87% (n=196) were in cohort A and 13% (n=29) in cohort B. In cohort A, 36.7% were females compared to 27.6% in cohort B. Median age in both cohorts was 76 years (range: 70-90 years in cohort A) (range: 72-86 years in cohort B). Overall, 26% of the patients had adverse risk disease as defined by European Leukemia Net (ELN) classification in cohort A and 51.7% in cohort B. Baseline characteristics are described in Table 1. Overall response rate (ORR) of the entire cohort was 43.6% (n=92) (Table 2). ORR in cohort A was 25.5% (n=47) compared to 66.7% (n=18) in cohort B (p

Description: Introduction: Acute myeloid leukemia (AML) is a heterogeneous disease with varied outcomes dependent on patient cytogenetic and mutational status. Thirty percent of adults with newly diagnosed AML have a mutation in the fms-related tyrosine kinase 3 (FLT3) gene. Midostaurin is a small molecule inhibitor that acts on multiple receptor tyrosine kinases, including FLT3. The RATIFY trial showed improved overall survival (OS) and event-free survival in patients treated with daunorubicin and cytarabine (7+3) plus midostaurin (Stone et al, NEJM 2017). In this trial, a dose of daunorubicin 60 mg/m2 was administered. High dose (HD) 90 mg/m2 daunorubicin significantly improved the rate of complete remission and overall survival, including in patients with FLT3-ITD (Luskin et al, Blood 2016). HD daunorubicin has also been shown to be more effective than idarubicin in patients with FLT3-ITD AML (Lee et al, J Clin Oncol 2017). This data raises the question of whether the combination of midostaurin and HD daunorubicin would further improve outcomes of FLT3 mutated AML patients, while maintaining a tolerable safety profile. The objective of this study is to describe the safety and efficacy endpoints of FLT3 mutated AML patients treated with HD daunorubicin plus midostaurin as part of induction therapy. Methods: We retrospectively reviewed clinical and molecular data of patients at Memorial Healthcare System, Moffitt Cancer Center, and Sylvester Cancer Center with newly diagnosed FLT3 mutated AML treated from May 1st, 2017 to July 1st, 2019. Clinical data was abstracted in accordance with institutional review board approved protocol. All patients were induced with HD daunorubicin 90 mg/m2 on days 1-3, cytarabine 100 mg/m2 on days 1-7, and midostaurin 50 mg PO twice daily on days 8-21. Growth factor and antimicrobial support were used per institutional guidelines. Demographics were analyzed using descriptive statistics. OS was analyzed using Kaplan Meier method. Other efficacy outcomes were CR, CRi (assessed according to the European Leukemia Network Criteria for AML), proportion of patients needing re-induction, and proportion of patients who underwent hematopoietic stem cell transplant (HSCT). Safety outcomes were adverse events (AEs) and early (30- and 60-day) mortality. Results: Twenty-six patients were included in the final analysis. Patient characteristics are outlined in TABLE 1. All patients were FLT3 mutated, as confirmed with molecular studies. The FLT3 subtype was ITD (high) in 3 patients, ITD (low) in 16 patients, TKD in 5 patients, and both in 2 patients. Seventy-seven percent of patients achieved a CR/CRi after one induction cycle, and 96.2% attained CR after two induction cycles. Median time to ANC and platelet recovery was 28 and 26 days, respectively. One patient died during the first 60 days, due to Enterococcus sepsis. The most common non-hematological AEs were nausea (77%), diarrhea (62%), mucositis (58%), rash (54%), and increased ALT (54%). Cumulative incidence of relapse in the cohort was 28% (n=7). Four patients relapsed pre-transplant and achieved CR2 with additional therapy. All 7 of these patients had co-occurring mutations of various types. Of the 20 patients who were considered transplant eligible, 13 (65%) underwent HSCT and 4 (20%) are pending transplant. Of the 13 transplanted patients, 3 experienced relapse post-transplant. After a median follow up of 14.5 months, median OS has not been reached. Conclusion: In our multi-center experience, induction with HD daunorubicin, cytarabine, and midostaurin is clinically effective and seems to be well tolerated. Short term mortality was low and AEs were manageable, with no unexpected safety signals. Also, CR/CRi rates were higher than previously reported, suggesting that the combination of HD daunorubicin and midostaurin may improve the outcomes of patients with FLT3 mutated AML. Future analyses with larger patient samples and longer follow up are warranted to further evaluate long-term safety and efficacy for this regimen. Figure Disclosures Sandoval-Sus: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Bradley:AbbVie: Other: Advisory Board. Talati:Agios: Honoraria; Celgene: Honoraria; Pfizer: Honoraria; Astellas: Honoraria, Speakers Bureau; Daiichi-Sankyo: Honoraria; Jazz Pharmaceuticals: Honoraria, Speakers Bureau. Watts:Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Sallman:Abbvie: Speakers Bureau; Novartis: Speakers Bureau; Jazz: Research Funding; Incyte: Speakers Bureau; Celyad: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding, Speakers Bureau. Sweet:Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Celgene: Speakers Bureau; Jazz: Speakers Bureau; Incyte: Research Funding; Pfizer: Consultancy; Stemline: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees. Lancet:Daiichi Sankyo: Consultancy, Other: fees for non-CME/CE services ; Agios, Biopath, Biosight, Boehringer Inglheim, Celator, Celgene, Janssen, Jazz Pharmaceuticals, Karyopharm, Novartis: Consultancy; Pfizer: Consultancy, Research Funding.

Description: Background: Patients with acute myeloid leukemia (AML) have dismal overall outcomes and survival is exceptionally poor in patients who experience relapse or are refractory (R/R) to frontline therapy. Since December 2018, combination therapy with hypomethylating agents (HMA) and venetoclax (HMA+Ven) has become standard frontline therapy for older patients or younger unfit patients. Moreover, it has been routinely utilized in patients experiencing relapsed or refractory AML yet response and outcome data is limited in patients with R/R disease. Thus, we investigated outcomes after HMA+Ven in patients with relapsed or refractory AML. Methods: We retrospectively annotated 72 patients who received treatment with HMA+Ven at Moffitt Cancer Center and Memorial Healthcare System between 2017 and 2019. Patients were divided into two subgroups: 1) initial remission therapy and 2) salvage therapy. Clinical and molecular data were abstracted in accordance with the Institutional Review Board approved protocol. Overall response rate (ORR) included patients achieving complete remission (CR), CR with incomplete count recovery (CRi), and morphologic leukemia free state (MLFS). Patients achieving CR, CRi, or MLFS were termed as responders (RES) and patients without CR, CRi, or MLFS were nonresponders (NRES). Fisher's Exact method was used to determine significance for categorical variables. Kaplan-Meier analysis was performed to determine median overall survival (mOS) and log-rank test was utilized to determine significance. All p-values are two-sided. Results: Out of 72 patients, 41 received HMA+Ven as initial therapy and 31 received it in the R/R setting. Baseline characteristics are outlined in Table 1. Median age was 63 years for patients with R/R AML with 58% female. In the R/R cohort, ORR was 34.5% with 0 (0%) patients achieving CR, 8 (27.6%) patients achieving CRi, and 2 (6.9%) achieving MLFS (Table 2). When compared to patients receiving HMA+Ven as initial therapy, ORR was significantly lower in the R/R cohort (64.1% vs. 34.5%, p=0.03). Among 31 patients in the R/R cohort, 6.5% (n=2) proceeded to allogeneic stem cell transplant (allo-SCT) after achieving CRi. European LeukemiaNet (ELN) risk stratification was known in 22 patients in the R/R cohort and ORR were similar in patients in the favorable/intermediate risk group (n=8) compared to adverse risk group (n=14) (37.5% vs. 28.6%, p=1.0). When compared to HMA+Ven used as initial therapy, ORR among the R/R cohort were not different among adverse risk groups (58.3% vs. 28.6%, p=0.10); however, ORR were significantly lower among patients with favorable/intermediate risk (100% vs. 37.5%, p=0.009). At a median follow-up of 7.6 months (mo), mOS was 4.9mo in the R/R cohort with mOS among RES superior to NRES (not reached vs. 2.4mo, p=0.0009) (Figure 1). Moreover, mOS was inferior in R/R patients compared to initial therapy (4.9mo vs. 13.8mo, p=0.0013) (Figure 2). A total of 15 (48.4%) patients had HMA exposure prior to receiving HMA+Ven without apparent impact on mOS (3.7mo (prior HMA) vs. 4.9mo (no prior HMA), p=0.97). The median duration of CR/CRi was 5.2mo and the median time to CR/CRi was 2.4mo. Based on ELN risk groups, mOS was not statistically different among patients with favorable/intermediate risk disease compared to adverse risk disease (8.6mo (fav/int) vs. 2.8mo (adverse), p=0.07). Responses were also analyzed based upon somatic mutations (Figure 2). In patients with isocitrate dehydrogenase 1 and 2 mutations (IDH1/IDH2) compared to patients without IDH1/2, ORR were 60% vs. 25%, respectively (p=0.28) with no significant difference in mOS (7.2mo (IDHmut) vs. 3.1mo (IDHwt), p=0.38). Comparing patients with TP53 mutation to those without TP53 mutations, no significant difference in ORR (25% vs. 33%, p=1.0) or mOS (4.4mo vs. 6.9mo, p=0.0.84) was noted. Conclusion: Although combination therapy with HMA+Ven has yielded impressive responses as frontline therapy, response rates with this combination in the salvage setting are less encouraging with the possible exception of those patients with IDH1/IDH2 mutations. Nevertheless, responders to salvage HMA+Ven had a significant survival benefit compared to nonresponders, suggesting that this combination is a reasonable salvage option in patients with relapsed or refractory AML. Disclosures Padron: Incyte: Research Funding. Kuykendall:Incyte: Honoraria, Speakers Bureau; Celgene: Honoraria; Janssen: Consultancy; Abbvie: Honoraria. List:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lancet:Agios, Biopath, Biosight, Boehringer Inglheim, Celator, Celgene, Janssen, Jazz Pharmaceuticals, Karyopharm, Novartis: Consultancy; Pfizer: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Other: fees for non-CME/CE services . Sallman:Celyad: Membership on an entity's Board of Directors or advisory committees. Komrokji:JAZZ: Speakers Bureau; JAZZ: Consultancy; Agios: Consultancy; DSI: Consultancy; pfizer: Consultancy; celgene: Consultancy; Novartis: Speakers Bureau; Incyte: Consultancy. Sweet:Abbvie: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Agios: 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; Celgene: Speakers Bureau; Jazz: Speakers Bureau; Incyte: Research Funding; Pfizer: Consultancy; Stemline: Consultancy. Talati:Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Daiichi-Sankyo: Honoraria; Astellas: Honoraria, Speakers Bureau; Pfizer: Honoraria; Celgene: Honoraria; Agios: Honoraria. OffLabel Disclosure: Venetoclax is approved in combination with hypomethylating agents (azacitidine or decitabine) or low dose cytarabine for treatment of newly diagnosed AML in adults aged 75 years or older, or those who have comorbidities that preclude the use of induction chemotherapy.

Description: Background: Patients with acute myeloid leukemia (AML) with myelodysplasia related changes (MRC) or therapy related myeloid neoplasm have poorer outcomes compared to patients with de novo AML. CPX-351 was approved by the Food and Drug Administration (FDA) in 2017 as an induction chemotherapy regimen for patients with AML-MRC or t-AML as defined by 2016 World Health Organization (WHO) classification. A large randomized phase 3 study that led to approval of CPX-351 included only the patients between age 60 and 75. However, the FDA approval extends to patients of age ≥18 years with limited data regarding its efficacy in a younger patient population. Methods: We performed a retrospective study of clinical and molecular data of 89 patients treated at Moffitt Cancer Center with CPX-351 as frontline induction chemotherapy regimen in patients with AML. Clinical data was abstracted in accordance with institutional review board approved protocol. Patients were then divided in two subgroups: Cohort A) Age

Description: Introduction: Liposomal daunorubicin and cytarabine (Vyxeos®) improves overall survival and remission rates compared to conventional daunorubicin and cytarabine (7+3) induction in older patients with secondary acute myeloid leukemia (AML). The safety profiles are similar, despite prolonged time to neutrophil and platelet count recovery with liposomal daunorubicin and cytarabine (Lancet et al, JCO 2018). There are other potential benefits of the liposomal combination, such as the feasibility of outpatient (OP) administration which can improve patient satisfaction and healthcare costs. Herein we show preliminary results of a pilot program based on OP liposomal daunorubicin and cytarabine administration to safely decrease inpatient (IP) days, with close OP monitoring throughout treatment phase until recovery. Methods: The objective of this study is to compare the IP hospital days between patients induced with liposomal daunorubicin and cytarabine in the Inpatient/Outpatient (IPOP) program vs. IP setting. The IPOP program involves administration of chemotherapy and close monitoring of patients in the OP setting who receive traditionally IP chemotherapy regimens. All patients received liposomal daunorubicin and cytarabine induction at a dose of daunorubicin 44 mg/m2 and cytarabine 100 mg/m2 via intravenous infusion over 90 minutes on days 1, 3 and 5. Patients were excluded for IPOP liposomal daunorubicin and cytarabine if they had signs or symptoms of active infection, cardiopulmonary disease, at risk for tumor lysis syndrome, ECOG 〉 2 or did not have an appropriate caregiver or transportation to the cancer center. Eligible patients received liposomal daunorubicin and cytarabine in the IPOP program and were monitored at least every other day until count recovery. Patients who developed complications such as febrile neutropenia were hospitalized with the goal of de-escalating antibiotic therapy and when appropriate, discharged to IPOP for continued care. Ineligible patients for IPOP treatment received IP liposomal daunorubicin and cytarabine induction and discharged to OP care prior to count recovery if clinically appropriate. A t-test of unequal variance was utilized to determine statistical significance between number of IP days between IPOP and IP groups. Results: Over the study period, 12 patients received induction therapy with liposomal daunorubicin and cytarabine. Seven patients (58%) received IPOP induction and 5 received IP induction (Median age: 72, 67 respectively). One patient was admitted prior to completing the third induction dose, the other six IPOP patients (86%) tolerated OP treatment well. All IPOP patients were eventually admitted, with median of 9 OP days prior to admission (range 4-17 days). All admissions were due to infectious complications: 5 were febrile neutropenia and one was due to a complicated skin/soft tissue abscess. Overall, the IPOP patients were only hospitalized for 46% of total days from start of induction until remission (CR, CRi, PR), progression, or recovery of neutrophils (≥500/µL) and platelets (≥50,000/µL). Mean cumulative days of IP and OP care were 19 and 22 days, respectively. Patients induced in the IP setting were hospitalized for 82% of their induction course with cumulative mean of 31 IP and 7 OP days. Mean cumulative IP hospital days was significantly less in the IPOP group as compared to the IP group (19 vs. 31 days, p=0.034). The overall response rate among the entire cohort was 75% (CR + CRi 50%) and was similar between the IPOP and IP groups. The median time to recover counts in patients who achieved CR + CRi was 36 days for both groups. The overall safety profile was similar between both groups. No patient died during the induction period and two patients successfully underwent hematopoietic stem cell transplantation. Two patients did not respond to therapy and both were eventually discharged with hospice care. Conclusions: In this pilot program, IPOP liposomal daunorubicin and cytarabine induction and management appears to be safe and to significantly reduce the length of hospitalization in patients with secondary AML. Future analyses with larger samples of patients are needed to further evaluate patient outcomes, safety and financial implications based on decreased inpatient hospital utilization. Disclosures No relevant conflicts of interest to declare.