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Liposomal daunorubicin/cytarabine (CPX-351) gained FDA approval for secondary AML after demonstrating improved outcomes over daunorubicin and cytarabine (7 + 3). A number of study limitations prompted a comparison of safety/efficacy of CPX-351 against regimens containing a purine analogue and high-dose cytarabine (HIDAC). This retrospective study compared complete response rates with/without count recovery (CR/CRi) between HIDAC-based regimens and CPX-351 in 169 patients with newly diagnosed sAML. The CR/CRi rate was 62.7% in the HIDAC-based therapy arm vs. 47.9% in the CPX-351 arm (

Secondary AML (s-AML) encompasses a distinct subgroup of AML with either therapy-related AML or AML arising from preexisting myeloid neoplasms. Despite recent advances in the treatment armamentarium of AML, outcomes remain poor in s-AML. The purpose of this review is to highlight distinct characteristics, prognostic factors, and treatment options for patients with s-AML. Further, we focus on a distinctly poor-risk subgroup of s-AML with previous exposure to hypomethylating agents (HMAs) and describe ongoing clinical trials in this patient population. CPX-351 (liposomal daunorubicin and cytarabine) is the first drug approved for s-AML and represents an advancement in the management of fit patients with this subtype of AML. Despite incremental improvement in remission rates and survival, long-term survival remains poor. Patients who have received prior HMAs for antecedent MDS rarely benefit from CPX-351 or other cytotoxic chemotherapy regimens. The approval of venetoclax in combination with azacitidine has led to a paradigm shift in the management of newly diagnosed older unfit AML patients; however, patients with s-AML and prior HMA therapy were excluded from the landmark randomized phase 3 study. Several early phase clinical trials with both low- and high-intensity therapies are ongoing for s-AML patients, though prior HMA exposure limits inclusion in many of these studies that include HMAs. Patients with s-AML previously treated with an HMA have dismal outcomes with standard therapeutic options and are under-represented in clinical trials. Trials investigating novel therapeutic options in this population are critically needed.

Introduction Over the past 40 years, therapy intensification has continuously contributed to an improvement in the prognosis of children with AML. Hence, the AML-BFM 2004 trial resulted in a 5-year overall survival rate (OS) of 70%. Similar outcomes backing this claim were obtained by other study groups. During the prospective, randomized AML-BFM 2012 trial, purine analogue clofarabine (C) was introduced to the therapy regimen. Prev. synergistic effects of C combined with cytarabine (A) have been observed in relapsed/refractory ped. AML. It was meant to further increase the antileukemic efficacy in the 1st induction of de novo AML. Clofarabine (C), liposomal daunorubicin (Dx; L-DNR), and cytarabine (A) were randomized against to the stand. induction course of cytarabine, etoposide (E), and L-DNR. The implementation of a stand. stem cell transplantation (SCT) indication for patients with HR AML was another progress. The trials' primary obj. was the improvement of event-free survival (EFS) in ped. AML. Patients and Methods AML-BFM 2012 was an open, interventional, multi-center, prospective, randomized clinical trial for patients with de-novo childhood AML (age Results With a 3-yr OS of 82 ± 3% & 3-yr EFS of 69 ± 4%, respectively, children treated by AML-BFM 2012 have an excellent outcome (median FU: 3.03 yrs.), which is superior to previous trials. The outcome did not significantly differ between ADxE and CDxA. In the study n=9 early deaths (EDs; defined as death Two statistical simulations were used to determine the potential significance of the study's primary obj., if 500 patients had been enrolled. In both simulations, the same progress was assumed for the patient outcome, only extrapolated to the required no. of cases. In the 1st simulation, the actual randomization compliance was retained in favor of the stand. arm ("as treated" simulation). In the 2nd calculation, therapy groups were weighted according to the planned intent-to-treat ratio of 1:1 ("intent to treat" simulation). Various simulated case nos. were translated into whole nos. to fulfill the criteria for the Kaplan-Meier analysis. Neither calculation shows a major effect on EFS or OS for either arm. Conclusion The treatment regimen used in AML-BFM 2012 has an excellent overall outcome, which exceeded outcomes from previous trials. The outcome is not only a result of the intro. of C, despite its potential effectivity in ped. AML. The results are closely linked to a better risk group stratification, improvements of allogeneic SCT in HR patients, and better supportive care. Since L-DNR was successfully evaluated in ped. AML in first and second-line treatment (AML-BFM Study 2004 (Creutzig et al. 2013) / Int. Relapsed AML 2001/01 (Kaspers et al. 2013)), incl. a possible reduction of anthracycline-induced cardiomyopathies, the unavailability of L-DNR due to industrial reasons resulted in severe damage in the treatment devel. in children with malignancies. More early clinical trials are vital to further examine other neoadjuvant drug combs. that replace L-DNR. In summary, AML-BFM 2012 showed an improvement of EFS and OS. Forced termination of clinical trials for commercial reasons is ethically dubious. Pharmaceutical companies need to act responsibly regarding clinical trials involving sick children. The introduction of C as the first-line treatment of ped. AML should be considered feasible. Disclosures Reinhardt: Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; CLS Behring: Research Funding; bluebird bio: Membership on an entity's Board of Directors or advisory committees; Roche: Research Funding. OffLabel Disclosure: Clofarabine, Etoposide, liposomal Daunorubicine using in AML frontline treatment in children

Introduction:The design of advanced drug delivery systems based on synthetic and supramolecular chemistry has been very successful. Liposomal doxorubicin (Caelyx®), and liposomal daunorubicin (DaunoXome®), estradiol topical emulsion (EstrasorbTM) as well as soluble or erodible polymer systems such as pegaspargase (Oncaspar®) or goserelin acetate (Zoladex®) represent considerable achievements.Discussion:As deliverables have evolved from low molecular weight drugs to biologics (currently representing approximately 30% of the market), so too have the demands made of advanced drug delivery technology. In parallel, the field of membrane trafficking (and endocytosis) has also matured. The trafficking of specific receptors i.e. material to be recycled or destroyed, as well as the trafficking of protein toxins has been well characterized. This, in conjunction with an ability to engineer synthetic, recombinant proteins provides several possibilities.Conclusion:The first is using recombinant proteins as drugs i.e. denileukin diftitox (Ontak®) or agalsidase beta (Fabrazyme®). The second is the opportunity to use protein toxin architecture to reach targets that are not normally accessible. This may be achieved by grafting regulatory domains from multiple species to form synthetic proteins, engineered to do multiple jobs. Examples include access to the nucleocytosolic compartment. Herein, the use of synthetic proteins for drug delivery has been reviewed.

Introduction With novel treatment strategies for acute myeloid leukemia becoming more readily utilized in the clinical practice setting, new data on potential treatment-related adverse events also has become available. Case report We present a patient case on a previously unreported potential adverse event related to liposomal daunorubicin-cytarabine administration. The patient experienced bilateral discoloration of the palms of his hands that resolved after completion of the treatment cycle, only to recur at cycle two of therapy. Management and outcome: No intervention was required as the condition resolved within a week of onset. Discussion With newer therapeutic modalities becoming more used in the clinical setting, it is important to understand the potential risks of treatment-related adverse events that come with them. To our knowledge this is the first case reporting blue-skin discoloration related to liposomal daunorubicin-cytarabine.

The emergence of coronavirus disease 2019 (COVID-19) has created new challenges in the management of serious diseases. We describe a 41-year-old male who presented with fever, watery diarrhea, and epistaxis. Initial workup revealed pancytopenia with >50% blasts on the peripheral smear raising suspicion of acute myeloid leukemia (AML) (later confirmed by bone marrow biopsy as AML with myelodysplasia-related changes) and a positive polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the extraordinary risk, he was treated with remdesivir and convalescent plasma for COVID-19. On admission day 8, repeat PCR for SARS-CoV-2 returned negative and the patient was deemed stable for chemotherapy. Therefore, induction was done with liposomal daunorubicin and cytarabine. However, he did not respond to the therapy and was started on re-induction therapy with decitabine and venetoclax. In our discussion, we review the current principles of treatment of patients with concurrent COVID-19 and AML.

Survival in children with relapsed/refractory a cute myeloid leukemia is unsatisfactory. Treatment consists of one course of fludarabine, cytarabine and liposomal daunorubicin, followed by fludarabine and cytarabine and stem-cell transplantation. Study ITCC 020/I-BFM 2009-02 aimed to identify the recommended phase II dose of clofarabine replacing fludarabine in the abovementioned combination regimen (3+3 design). Escalating dose levels of clofarabine (20-40 mg/m²/day x 5 days) and liposomal daunorubicin (40-80 mg/m²/day) were administered with cytarabine (2 g/m²/day x 5 days). Liposomal DNR was given on day 1, 3 and 5 only. The cohort at the recommended phase II dose was expanded to make a preliminary assessment of anti-leukemic activity. Thirty-four children were enrolled: refractory 1st (n=11), early 1st (n=15), ≥2ⁿd relapse (n=8). Dose level 3 (30 mg/m² clofarabine; 60 mg/m² liposomal daunorubicin) appeared to be safe only in patients without subclinical fungal infections. Infectious complications were dose-limiting. The recommended phase II dose was 40 mg/m² clofarabine with 60 mg/m² liposomal daunorubicin. Side-effects mainly consisted of infections. The overall response rate was 68% in 31 response evaluable patients, and 80% at the recommended phase II dose (n=10); 22 patients proceeded to stem cell transplantation. The 2-year probability of event-free survival (pEFS) was 26.5±7.6 and probability of survival (pOS) 32.4±8.0%. In the 21 responding patients, the 2-year pEFS was 42.9±10.8 and pOS 47.6±10.9%. Clofarabine expo-sure in plasma was not significantly different from that in single-agent studies. In conclusion, clofarabine was well tolerated and showed high response rates in relapsed/refractory pediatric acute myeloid leukemia. Patients with (sub)clinical fungal infections should be treated with caution. Clofarabine has been taken forward in the Berlin-Frankfurt-Münster study for newly diagnosed acute myeloid leukemia. The Study ITCC-020 was registered as EUDRA-CT 2009-009457-13; Dutch Trial Registry number 1880. CA extern

Background: Liposomal daunorubicin/cytarabine (CPX-351) and hypomethylating agent+venetoclax (HMA+V) have shown survival advantage as frontline therapies for older and biologically adverse AML. Although HMA+V is approved for chemotherapy ineligible pts, there is increased use of the combination in older fit pts. with biologically adverse AML. However, clinical outcomes between the two treatments have not been compared and will have a major clinical impact. Our aim was to compare CPX-351 vs HMA+V as upfront treatment for newly diagnosed AML using a multi-center retrospective study. Methods: This is a multicenter retrospective study drawing from 4 large U.S. academic medical centers (Weill Cornell, Northwestern, Moffitt, Memorial Sloan Kettering). Eligibility included pts who received either CPX-351 or HMA+V as frontline therapy for AML. Response was determined using ELN 2017 guidelines. To evaluate the association between treatment type and categorical factors of interest, and the primary outcome variable of treatment response, the chi-square test or Fisher's exact test was used. For the outcome variable of bone marrow response status, multivariable logistic regression analysis was performed. For the relapse free survival (RFS) and overall survival (OS) outcomes, Kaplan-Meier survival analysis was performed, and the log-rank test was employed to compare between categories of treatment-type and prognostic factors of interest. Multivariable cox proportional hazards regression analysis was performed to assess the independent effect of treatment and demographic/prognostic factors of interest on outcomes of RFS/OS. Results: Our study included 211 CPX-351 and 226 HMA+V treated pts. 11 pts were excluded due to missing age or ELN risk. Pt. characteristics and univariate analyses are summarized in Table 1 and 2. Overall CR+CRi rates, median RFS and OS for CPX-351 vs. HMA+V were 57.8% vs. 56.6%, 32.5 vs. 14.1 months (p=0.11) and 17.3 vs. 11.1 months (p=0.007). In multivariable analysis, after adjusting for age, ELN risk, prior myeloid malignancy, and prior HMA therapy, there was no difference between CPX-351 vs. HMA+V in CR+CRi (HR 1.32, p=0.23, 95% CI 0.8-2.1) and RFS (HR 0.92, p=0.75, CI 0.59-1.46). There was a significant difference favoring CPX-351 for OS (HR 0.74, p=0.04, CI 0.55-0.99). When analyses were restricted to pts aged 60-75 years (n= 152 CPX-351, n= 100 HMA+V), rates of CR+CRi were 59.2% vs. 54.0% (p=0.41), and median RFS and OS for CPX-351 vs. HMA+V treated pts was 32.5 vs. 13.3 months (p= 0.80) and OS 17.1 vs. 10.3 months (p=0.12). Multivariable analysis after adjusting for above variables showed no difference in CR+CRi, RFS and OS between CPX-351 vs. HMA+V (CR+CRi: HR 1.28, p=0.55, 95% CI 0.77-2.27, RFS: HR 0.70, p=0.17, CI 0.42-1.17 and OS: HR 0.80, p=0.20, CI 0.57-1.12). Multivariable subgroup analyses demonstrated significant advantage favoring CPX-351 for RFS in TP53 mutated pts (HR 0.37, 95% C.I. 0.14-0.96, p=0.04). Subgroup analyses for OS are summarized in Figure 2. Among patients where minimal residual disease (MRD) data was available (n=93 CPX-351, n=133 HMA+V), MRD negativity by flow was 34.4% (n=32) and 39.1%(n=52) for CPX-351 and HMA+V pts, respectively (p=0.47). Among pts aged 60-75 years, 47.7% and 19% of patients underwent HSCT in CPX-351 and HMA+V groups (p Conclusion: Our analysis demonstrated significant difference in OS favoring CPX-351 in the overall cohort and in several clinical subgroups, while no difference in CR+CRi and RFS was seen. The survival advantage in the CPX-351 group may be due to higher HSCT rates in CPX-351 treated pts. Among pts that did not proceed to HSCT, there was no difference in CR+CRi, RFS and OS between the treatment groups. We suspect that greater HSCT rates in the CPX-351 cohort were due to fewer comorbidities among CPX-351-treated pts or other biases, and comorbidity analyses are pending and will be reported. Figure 1 Figure 1. Disclosures Ritchie: Bristol Myers Squibb: Consultancy, Research Funding; Abbvie: Consultancy, Honoraria; NS Pharma: Research Funding; Novartis: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria; Protaganist: Consultancy, Honoraria; Astellas: Consultancy, Research Funding; Incyte: Consultancy, Honoraria, Speakers Bureau; ARIAD Pharmaceuticals: Ended employment in the past 24 months, Speakers Bureau; Jazz: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Celgene/BMS: Consultancy, Other: travel support, Speakers Bureau. Lee: Pin Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Innate: 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; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees. Goldberg: Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Arog: Research Funding; Aprea: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Prelude Therapeutics: Research Funding; Aptose: Consultancy, Research Funding; DAVA Oncology: Honoraria; Celularity: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Dinner: Pfizer: Consultancy, Honoraria; Kite/Gilead: Consultancy, Honoraria. Sweet: AROG: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, 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; Gilead: Membership on an entity's Board of Directors or advisory committees. Roboz: Novartis: Consultancy; Bristol Myers Squibb: Consultancy; Glaxo SmithKline: Consultancy; Jazz: Consultancy; Astex: Consultancy; Blueprint Medicines: Consultancy; Mesoblast: Consultancy; Astellas: Consultancy; AstraZeneca: Consultancy; Pfizer: Consultancy; Bayer: Consultancy; Otsuka: Consultancy; Celgene: Consultancy; Daiichi Sankyo: Consultancy; Janssen: Consultancy; Jasper Therapeutics: Consultancy; Roche/Genentech: Consultancy; Helsinn: Consultancy; Amgen: Consultancy; MEI Pharma - IDMC Chair: Consultancy; Agios: Consultancy; Actinium: Consultancy; AbbVie: Consultancy; Janssen: Research Funding. Desai: Agios: Consultancy; Kura Oncology: Consultancy; Takeda: Consultancy; Astex: Research Funding; Bristol Myers Squibb: Consultancy; Janssen R&D: Research Funding.

Background: Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with a poor prognosis in the adult population, despite recent advancements in treatment paradigm. Induction with the liposomal formulation of cytarabine and daunorubicin (CPX-351) which has been shown in phase III trials to improve the median overall survival (OS) compared to standard induction (9.6 versus 5.9 months, respectively) and is FDA approved for patients therapy related AML or AML with myelodysplasia-related changes. Hypomethylating agents (HMA) (azacitidine and decitabine) have recently garnered renewed attention in combination with the BCL-2 inhibitor venetoclax (VEN). Azacitidine with venetoclax demonstrated a median overall survival of 16.9 months in those that were deemed ineligible for intensive induction. While these trials were inherently different patient populations, in clinical practice, physicians must often choose between these two therapies in the frontline setting. Thus, we aimed to examine patient characteristics and respective outcomes with these two treatment approaches. Methods: This was a retrospective cohort studies of patients diagnosed with AML and treated at Virginia Commonwealth University/Massey Cancer Center as identified by our data analytics core between June of 2018 and December of 2020. Data was extracted and manually verified from the electronic medical record into an AML database instrument created in RedCap. Statistical analysis was then performed using GraphPad Prism. Descriptive analyses were conducted for demographics and baseline clinical characteristics, and OS rates were evaluated using Kaplan-Meier analyses and compared using log-rank test. Results: A total of 160 patients with AML were identified. Of those, 58 were treated with either HMA/VEN (N = 43) or CPX-351 (N = 15) in the frontline setting. Median age of patients treated with HMA/VEN was 72 (range: 37 - 85) compared to the median age of 69 (range: 44 - 72) for the CPX-351 group, which was statistically significant (p = 0.002). There was no statistical difference in other demographic characteristics such as sex (p = 0.380), race (p = 0.323), Charleston Comorbidity Index (p = 0.097), or ECOG score (p = 0.126). AML risk stratification based on molecular and cytogenetic data per ELN 2017 also did not differ between the two groups (p = 0.230), with both groups having numerically similar adverse-risk patients (86.7% in the CPX-351 cohort and 70.7% in the VEN cohort). Figure 1 demonstrates a Kaplan-Meier analysis, which revealed a median OS in the VEN group of 281 days (9.23 months) compared to a median OS in the CPX-351 group of 713 days (23.4 months), which was not significant (p = 0.109). Additionally, there was no difference in the OS when only the adverse cytogenetic categories were analyzed from each cohort (Figure 2, p = 0.058). There was one (6.7%) death within 30 days in the CPX-351 group and no deaths within 60 days, compared to one (2.3%) death within 30 days and 9 (20.9%) deaths within 60 days in the VEN group, which was not significantly different (p = 0.257). Allogeneic stem cell transplant was more common in the CPX-351 group (40%) than the VEN group (4.7%) (p = 0.0007). Conclusion : Although these regimens were intended for diverging populations of induction versus non-induction candidates, there is clinical overlap in physician discretion regarding both regimens. Our data shows similar baseline characteristics between these two groups, though the VEN cohort was slightly older. Our data demonstrated that in the CPX-351 cohort, the OS was longer, there appeared to be fewer deaths during induction, and more patients proceeded to transplant - though the former approached statistical significance, particularly when matched with adverse cytogenetic risk (p = 0.058). This argues for continued use of intensive regimen for those who are candidates, especially those in whom allogeneic hematopoietic stem cell transplant is being considered. Prospective studies between these regimens is warranted. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Introduction: Despite uninterrupted efforts made to develop newer drugs and schedules in the treatment of acute myeloid leukemia (AML), the induction of chemotherapy with cytarabine and an anthracycline (the classical ‘7 + 3’) still remains the standard of care. Unfortunately, many patients are not suitable for intensive induction therapy due to poor prognosis, age and comorbidities. For these challenging populations, the clinical outcome is poor and novel approaches are desperately required. One of these approaches is the liposomal formulation of drugs, allowing the delivery of more drug to the disease site and thereby improving efficacy and reducing toxicity. CPX-351 is a liposomal formulation of the cytotoxic drugs cytarabine and daunorubicin at synergistic concentrations.Area covered: In this article, we review the preclinical and clinical experience to date with CPX-351 for patients with AML. Phase I and II studies have been published and a randomized prospective phase III study has recently ...

Introduction: Liposomal daunorubicin and cytarabine (CPX-351) was approved based on data which showed improved overall survival (9.56 v 5.95 months; p = .003) and remission rates (47.7% v 33.3%; p = .016) compared to conventional cytarabine and daunorubicin (7+3) chemotherapy in older patients with newly diagnosed secondary acute myeloid leukemia (sAML). Patients receiving CPX-351 had prolonged time to neutrophil and platelet count recovery compared to 7+3, which was not associated with adverse outcomes (Lancet et al, JCO 2018). Based on these data, our center adopted CPX-351 as a first-line agent in this patient population. Considering the significant cost differences and delays in count recovery, we conducted a comparison of outcomes in patients who received CPX-351 versus 7+3 at our center. Methods: The objective of this study was to compare efficacy and safety of CPX-351 versus 7+3 in patients with sAML. Primary outcome was response rate as defined by CR or CRi. Secondary outcomes included duration of neutropenia, incidence of invasive fungal infections (IFIs), and number of patients proceeding to allogeneic hematopoietic cell transplant (HCT). Patients with sAML receiving induction with 7+3 (daunorubicin dosed at 60 or 90 mg/m2 per treating physician's discretion) or CPX-351 from July 2014 to April 2020 were reviewed. Secondary AML was defined as: AML with a history of myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML), AML with myelodysplasia-related changes, or therapy-related AML. Patients with prior myeloproliferative neoplasms, myelofibrosis, or FLT3 mutations were excluded. Patient characteristics were summarized using descriptive statistics (TABLE 1) including mean for continuous measures and proportions and frequencies for categorical measures. The association between continuous variables and patient groups were assessed using ANOVA or Student's t-test. The associations between categorical variables and patient groups were evaluated using Chi-square test. Results: Over the study period, 65 patients with sAML received induction therapy with either CPX-351 (n = 31) or 7+3 (n = 34). Of these, 61 patients had an evaluable bone marrow biopsy at count recovery. The data is summarized in Table 2. The response rates (CR or CRi) were no different (36% 7+3 vs 36% CPX-351, p = 0.958) among the study population. Longer duration of neutropenia was observed with CPX-351 (33 days 7+3 vs 47 days CPX-351, p = 0.026). More patients in the 7+3 arm proceeded to allogeneic HCT; however, this was not statistically significant (59% 7+3 vs 39% CPX-351, p = 0.105). In an efficacy subgroup analysis of patients with TP53 mutation, there was no difference in response rates (33% 7+3 vs 11% CPX-351, p = 0.224). There was no difference in IFI between the groups (38% 7+3 vs 42% CPX-351, p = 0.761). Upon further analysis of IFI characteristics, there was no difference in choice of mold-active vs non mold-active prophylaxis (ppx) and the incidence of IFIs (40% mold ppx vs 39% non-mold ppx, p = 0.91). Patients with baseline neutropenia prior to induction did not have increased risk of IFIs (65% 7+3 vs 74% CPX-351, p = 0.626). Additionally, there were no between group differences in incidence of IFIs in patients who were neutropenic prior to induction. Conclusions: In the evaluable dataset of patients receiving 7+3 or CPX-351, there was no difference in CR/CRi rate between the two subgroups. There was a longer duration of neutropenia in the CPX-351 group without increased incidence of IFI. However, we report a higher incidence of IFI compared to the study population in Lancet et al (18% Lancet vs 40% Miami) despite appropriate anti-fungal prophylaxis, which may be due to patient selection on the clinical trial, demographic differences (e.g., age, ethnicity), or locoregional environmental factors. In our population, a greater percentage of patients who received 7+3 proceeded to allogeneic HCT. While this study was not powered to detect a significant difference between the two regimens and these findings require validation in larger cohorts, they do not support superior outcomes in patients who receive CPX-351. Data on differences in hospital costs will also be presented. Future directions include a larger multi-center real-world analysis to evaluate patient outcomes, safety, and the financial implications of these two regimens. Disclosures Watts: Genentech: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Rafael Pharma: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Aptevo Therapeutics: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees.

The "7+3" regimen is recommended for treatment in patients with new diagnosis of acute myeloid leukemia (AML) who are fit for intensive chemotherapy. Patients with secondary AML (sAML) [i.e. AML evolving from antecedent hematologic disorders (AHD-AML) or after previous exposure to chemo/radiation therapy for unrelated cancer (t-AML)], have inferior outcomes with "7+3" regimen. A recent phase 3 study demonstrated superior CR rates and overall survival (OS) with upfront use of CPX-351 compared to "7+3" regimen in older patients (≥60 years) with sAML (Lancet et al JCO 2018). The combination of HMA+Ven is FDA approved for upfront treatment in newly diagnosed AML patients > 75 or those unfit for intensive chemotherapy based on CR+ CRi rates of 67% and median OS of 17.5 months. Herein, we compared the outcomes of older patients with sAML who received upfront treatment with either HMA+Ven or CPX-351 at our institution. Our analysis includes 47 consecutive patients with previously untreated sAML treated between 2018-2020 . Patients were treated with either HMA+Ven (n=27) or CPX-351 (n=20) based on physician preference. WHO criteria were used for the diagnosis AHD-AML and review of medical records for documenting exposure to leukemogenic agent for t-AML. Complete remission (CR) was defined by presence of 1000/µL and platelets ≥100,000/µL) were defined as CRh (hematologic recovery) and CR without blood count recovery as CRi (incomplete blood count recovery). Minimal residual disease (MRD) assessment was done on day-28 BM aspirate using multiparametric flow cytometric assay with lower limit of sensitivity of 0.01%. Patients demographic and disease features are summarized in Table 1. Mean age (p=0.39), mean blast percentage in BM aspirate (P=0.82), high-risk cytogenetics (P=0.37) and high-risk molecular mutations (P=0.737) were similar in both treatment groups. Of the 27 cases of sAML in HMA+Ven group, 8 were t-AML arising after prior chemotherapy (Hodgkin's Disease n=2; paraganglioma, desmoid tumor, breast cancer, NHL, multiple myeloma, ALL: one each) while 19 were AHD-AML. In CPX-351 group, 6 cases were t-AML arising after prior chemotherapy (NHL n=2, breast cancer n=2, T-Lymphoblastic Lymphoma and colon cancer one each) while 14 were secondary to AHD. The mean number of cycles were 3.3 (range 1-18) in HMA+Ven group and 1.45 (1-3) in CPX-351 group. Two-sample t test was used to compare continuous and normally distributed covariates, such as age and BM blasts, between HMA+Ven or CPX-351 arms. Pearson Chi-square or Fisher exact test was used to assess the associations between treatment and clinical outcomes. Kaplan-Meier method and log-rank test were used to assess OS or LFS. A P value of ≤ 0.05 was considered as statistically significant. The CR rate in patients treated on HMA+Ven group was 78% (n=21; 95% CI: 58-91%) vs 50% (n=10; 95% CI: 27-73%) in CPX-351 group (P=0.047). CRi was achieved in 52% (n=14) patients in HMA+Ven group compared to 25%(n=5) patients in CPX-351 group(p=0.064). MRD negative remission was achieved in 52% (n=14) patients in HMA+Ven group and in 25% (n=5) patients in CPX-351 group (p=0.064). In HMA+Ven group, 52% patients (n=14) achieved remission after one cycle of therapy compared to 45% (n=9) patients in CPX-351 arm (p=0.642). With a median follow-up of 6.7 months for all patients, the median leukemia free-survival (LFS) for HMA+Ven vs CPX-351 treatments is 16.2 vs NA months (P = 0.098) and the median OS is 13.2 vs NA months (P = 0.395). Ten patients in each group (37% in HMA+Ven and 50% in CPX-351; p=0.47) underwent allo-HCT. At last follow up, 14 patients (52%) have died in HMA+Ven group from: relapsed AML (n=10), sepsis (n=2), congestive heart failure (n=1) and unknown (UK) in one patient, whereas in CPX-351 group, 8 patients (40%) have died from relapsed AML in (n=5), respiratory failure (n=2) and UK causes in one patient. In patients resistant to initial therapy, the median OS is 3.5 vs 6.0 months between HMA+ Ven and CPX-351 groups (P = 0.224). Conclusion: In patients presenting with sAML, upfront treatment with HMA+Ven is feasible and associated with significantly better CR rates and a favorable trend for higher rates of negative MRD compared to CPX-351. A randomized prospective trial in patients with sAML is warranted to determine the most effective frontline regimen in this high-risk AML subgroup. Disclosures Salhotra: Celgene: Research Funding; Kadmon: Membership on an entity's Board of Directors or advisory committees. Al Malki:Rigel Pharma: Consultancy; Neximmune: Consultancy; Jazz Pharmacuticals, Inc: Consultancy. Aribi:Seattle Genetics: Consultancy. Ali:Incyte Corporation: Consultancy. Budde:Gilead Sciences: Consultancy; Merck: Research Funding; Amgen: Research Funding; Kite, a Gilead Company: Consultancy; Mustang Therapeutics: Research Funding; AstraZeneca: Research Funding; Roche: Consultancy. Dadwal:Ansun Biopharma: Research Funding; Karius: Research Funding; Shire/ Takeda: Research Funding; Gilead: Research Funding; Merck: Consultancy, Honoraria, Other: Advisory board meeting, Research Funding, Speakers Bureau; Chimerix: Research Funding; Janssen: Other: Advisory board meeting; Astellas: Speakers Bureau. Nakamura:NapaJen Pharma: Consultancy; Kadmon Corporation: Other: Advisory board meeting; Viracor: Consultancy; Magenta Therapeutics: Other: Advisory board meeting; Celgene: Other: Support on seminar; Kyowa-Kirin: Other: Support on a meeting presentation; Alexion: Other: Support on a meeting presentation; Merck: Other: advisory board meeting. Stein:Amgen: Consultancy, Speakers Bureau; Stemline: Consultancy, Speakers Bureau. Marcucci:Takeda: Other: Research Support (Investigation Initiated Clinical Trial); Merck: Other: Research Support (Investigation Initiated Clinical Trial); Iaso Bio: Membership on an entity's Board of Directors or advisory committees; Abbvie: Speakers Bureau; Novartis: Speakers Bureau; Pfizer: Other: Research Support (Investigation Initiated Clinical Trial). Pullarkat:Dova: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genetech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie, Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. OffLabel Disclosure: off label use of HMA+venetoclax in secondary AML

Introduction Liposomal daunorubicin/cytarabine (Vyxeos® or lipo-CD) is a dual drug liposomal encapsulation, delivering these drugs at a fixed 1:5 synergistic ratio for a longer therapeutic period. Compared to standard 7+3, lipo-CD pts had improved survival and remission rates in a pivotal phase III study, with more reaching allogeneic transplantation (HCT), with lower post-HCT mortality and improved survival. With its enhanced pharmacokinetics, lipo-CD may provide a potent bridge to second transplant for early relapses after HCT. Here, we report our experience. Methods We retrospectively reviewed recipients of lipo-CD at our institution since FDA approval 8/2017. Of 23 pts, 8 relapsed Results Median age was 60 yrs. They received 1-4 lines of therapy (median 2) prior to first HCT with 5/8 pts having received 7+3 (cytarabine 100-200mg/m2 × 7 days + dauno 60-90mg/m2 × 3 days). 6 had adverse cytogenetics/genomic profiles. 7/8 had AML and 1 high grade MDS. Pts relapsed at 2 to 7 mo (median 4 mo) after first HCT, and all 8 received full lipo-CD induction (dauno 44 mg/m2 and cytarabine 100 mg/m2 on Days 1, 3, and 5) as outpatient therapy. [Table] 7/8 had Day 14 bone marrow biopsies: 3 were clear, 2 had >80% cytoreduction, and 2 had similar blast count. 3 with persistent disease underwent re-induction with lipo-CD (Days 1 and 3). All successfully proceeded to second transplant at 15-70 days after lipo-CD: 7 with same donor after melphalan 140mg/m2, and 1 from a different donor after busulfan/fludarabine. Tacrolimus was started on day + 7 and discontinued at day + 28 if no GVHD. 4/8 remain alive. 2 relapsed at 3 and 6 months post-HCT and are remarkably in CR at 19 and 16 mo after second transplant despite isolated CNS relapses, which were successfully treated. The other two relapsed at 2 and 3 mo post-HCT and are alive after second transplant. Conclusion Outpatient lipo-CD as a bridge to second transplant is feasible and effective in treating AML/MDS with early relapse after first HCT. While preliminary, survival appears favorable to that reported (14-23% at 1 year) in this very poor risk group, including those with adverse cytogenetics. Prospective multi-center trials are planned.

The prognosis of adult acute myeloid leukemia (AML) remains poor, with the long-term survival rate less than 50%. However, the current paradigms of treatment are changing through a better understanding of the disease genetics and pathophysiology. Since 2017, eight new drugs have been approved by the U.S. Food and Drug Administration for the treatment of AML, including the FLT3 inhibitors midostaurin and gilteritinib, the IDH inhibitors ivosidenib and enasidenib, the anti-CD33 monoclonal antibody gemtuzumab ozogamicin, liposomal daunorubicin and cytarabine, the hedgehog pathway inhibitor glasdegib and the BCL-2 inhibitor venetoclax. Preclinical data demonstrated the anti-leukemic efficacy of venetoclax in AML and its synergy when combined with hypomethylating agents or chemotherapy agents. Clinical trials have demonstrated the clinical benefit of venetoclax-based therapies in newly diagnosed AML, leading to the recent FDA approval of venetoclax in combination with hypomethylating agents or low-dose cytarabine for older adults with newly diagnosed AML. Herein, we focus on the role of single-agent BCL-2 inhibition in AML and review the clinical studies of venetoclax-based combination regimens and the evolving mechanisms of resistance.

Context We have previously developed an Ara-CTP-SNP-Score (ACSS) composed of single nucleotide polymorphisms (SNP) of key genes within the pharmacokinetic pathway of cytarabine (Ara-C) that correlates with intracellular Ara-CTP levels and response to Ara-C therapy in pediatric AML patients. We hypothesize that genetic polymorphisms are also the basis of variability of response observed in elderly AML patients. Objective Our objective is to establish whether ACSS correlates with CR in elderly AML patients treated with Ara-C. Design We conducted a retrospective pilot study. Patients treated for AML between June 2010 and June 2018 were identified from our center's tissue database. Patients were eligible for inclusion in study if they were elderly (age >60), had AML treatment with standard dose Ara-C (200 mg/m2), and had donated a blood or bone marrow sample. Patient samples were genotyped for key genes within the Ara-C metabolic pathway (CTPS1-rs12067645, SLC28A3-rs17343066, DCK-rs4643786, RRM1-rs11030918). ACSS was determined for each patient based on model. Patients were classified as ACSS-High (score>0) or ACSS low (score Results Twenty-nine patients were genotyped; 15 patients were ACSS high, and 14 patients were ACSS low. Of ACSS high patients, 73% (n=11/15) had CR, and 27% (n=4/15) did not have CR. Of ACSS low patients, 36% (n=5/14) had CR, and 64% (n=9/14) did not have CR, p=0.0656. Of patients with ACSS high and CR, 72% (n=8/11) had intermediate risk cytogenetics, 19% (n=2/11) had poor risk cytogenetics, 9% (n=1/11) had favorable risk cytogenetics, 55% had s-AML, 63% (n=7/11) were treated with “7+3”, 18% (n=2/11) were treated with CLAG, 9% (n=1/11) were treated with liposomal daunorubicin + cytarabine, 9% (n=1/11) were treated with sequential 7+3, CLAG, CLA, and 27% (n=3/11) had prior HMA. Conclusions ACSS correlates with response to Ara-C chemotherapy in elderly patients with AML. Many patients who have ACSS high and respond to Ara-C have traditional risk factors for poor response to chemotherapy. A larger data set is needed to confirm these findings. ACSS may be a tool to identify patients who may benefit from Ara-C. Funding University of South Florida Graduate Medical Education Grant Program

Background Liposomal formulation of anthracyclines provide better systemic and organ-specific tolerance, with potential for less local tissue damage during extravasation. Several small series have reported that most liposomal anthracycline extravasations are consistent with irritant injury without tissue necrosis. There have been no reports published regarding the clinical effects of extravasation of liposomal cytarabine-daunorubicin (CPX-351). Case report The patient received CPX-351 for relapsed acute myelogenous leukemia via a left chest wall port-a-catheter. The catheter became dislodged. Once symptoms developed, the infusion was discontinued, with observations demonstrating an 8-cm region of edema, warmth, no erythema, and no drainage. Limited supportive management was performed. Physical examination the following day demonstrated no evidence of necrosis, and erythema resolved completely without additional intervention. Conclusion CPX-351 extravasation behaving as an irritant is consistent with the reports of other liposomal anthracyclines.

The extravasation of chemotherapeutic agents is a challenge for oncologic care teams. The management of nonliposomal (conventional) anthracyclines is well established in clinical practice guidelines, including general measures and specific antidotes, such as dexrazoxane. However, there is little scientific evidence on the management of liposomal and pegylated liposomal anthracyclines. The aim of this paper was to review the scientific literature on the extravasation of liposomal and pegylated liposomal anthracyclines and determine the clinical impact of this type of extravasation, focusing on dexrazoxane. The literature was searched using two databases: PubMed and Embase. Three searches were conducted, using liposomal anthracycline extravasation, pegylated liposomal anthracycline extravasation, and liposomal doxorubicin extravasation as keywords, respectively. Seven articles fulfilled the study eligibility criteria and included seventeen cases in humans. Extravasation occurred with three drugs: liposomal doxorubicin in nine (53%) patients, liposomal daunorubicin in four (23.5%) patients, and pegylated liposomal doxorubicin in four (23.5%) patients. General measures for extravasations were applied in all patients, but only three patients received dexrazoxane. All cases were completely resolved at 2-3 months, except for one patient, in whom dexrazoxane was not used. In animals, dexrazoxane decreased both the frequency of wounds produced by pegylated liposomal doxorubicin and their extent. The pharmacokinetic profiles of liposomal and pegylated liposomal anthracyclines differ from those of conventional anthracyclines, modifying their effectiveness and safety. General measures may be inadequate to heal areas affected by extravasation, which may require the administration of dexrazoxane. However, each case should be evaluated individually for the administration of dexrazoxane in off-label use until scientific evidence is available on its effectiveness and safety as an antidote for these formulations of anthracyclines.

Introduction: Liposomal daunorubicin/cytarabine (Vyxeos®) is a dual drug liposomal encapsulation of cytarabine and daunorubicin, delivering drugs at a fixed 5:1 synergistic ratio for a longer therapeutic period. Compared to standard 7+3, liposomal cytarabine/daunorubicin (lipo-cytara/dauno) patients had improved survival and remission rates in a pivotal phase III study of elder adults with high-risk acute myelogenous leukemia (AML). Furthermore, more lipo-cytara/dauno patients went to allogeneic stem cell transplantation (HCT), with lower mortality and improved survival compared to those induced with 7+3. With its enhanced pharmacokinetics, lipo-cytara/dauno may provide a potent bridge to transplant. We report our experience using lipo-cytara/dauno as a bridge to same donor lymphocyte infusion (DLI) or different donor HCT in high-risk AML. Methods: We retrospectively reviewed all patients who received lipo-cytara/dauno at our institution since the FDA approval in August 2017. Of the 21 patients who have been treated, 9 received it as a bridge to cell therapy. All patients received the drug by usual means under the FDA label. Results: The median age of the 9 patients who received lipo-cytara/dauno as a bridge to cell therapy was 59 years. Seven were male, and two were female. Patients had had 1-4 prior lines of chemotherapy (median 2) with 7 of 9 patients having received prior standard 7+3 induction (cytarabine 100-200 mg/m2 x 7 days infusion and daunorubicin 60-90 mg/m2 x 3 days). Most had adverse cytogenetics, and all 9 patients received full lipo-cytara/dauno induction (daunorubicin 44 mg/m2 and cytarabine 100 mg/m2 on Days 1, 3, and 5) as outpatient therapy [Table]. Of the 9 patients, 6 had AML with very early relapse after HCT, with median time to relapse of 4 months (range 3 to 7 months). All 6 successfully proceeded to their planned cell infusion: 5 received same donor DLI after melphalan at 140 mg/m2, and 1 underwent second HCT from a different donor with busulfan/fludarabine conditioning at Days 15-40 after lipo-cytara/dauno. Of the remaining 3, two had relapsed AML after an initial remission (one was in first complete remission (CR1) for 3 months after 7+3/midostaurin induction and the other was in CR1 for 7 months after 7+3 induction/high dose cytarabine consolidation) and one had primary refractory disease (PREF) after 7+3 and azacitidine/venetoclax induction regimens. All 3 successfully underwent first HCT at Days 15-100 days after lipo-cytara/dauno bridge. The PREF patient received fludarabine/cyclophosphamide/TBI conditioning followed by matched unrelated donor transplant. Of the 2 with relapsed AML after initial remission, one received busulfan/fludarabine/thiotepa conditioning followed by umbilical cord stem cell transplantation and the other patient received fludarabine/cyclophosphamide/TBI conditioning prior to matched related donor transplant. Six of 9 had Day 14 bone marrow biopsies after lipo-cytara/dauno: 2 were in CR, 2 had >80% cytoreduction, and 2 had similar blast count. Three with persistent disease underwent reinduction with lipo-cytara/dauno (Days 1 and 3) and proceeded straight to cell therapy after. Median days to hospitalization after outpatient lipo-cytara/dauno was 6 days (range 3 to 14 days). Four out of 9 patients remain alive. Two were very early post HCT relapses (relapsed at 3 and 6 months post-HCT), both of which are remarkably in CR at 14 and 17 months after second cell therapy. Interestingly, both had CNS relapse, which were successfully treated, and both remain alive and in remission today. The other two had relapsed AML and PREF AML and underwent first HCT after lipo-cytara/dauno bridge. They remain alive and in remission at 1 and 8 months. Conclusion: In this retrospective study, outpatient lipo-cytara/dauno as a bridge to cell therapy is feasible and effective in very high-risk AML with no other viable options. While preliminary, survival appears favorable to that reported elsewhere at 14-23% at 1 year in this poor risk group, including those with adverse cytogenetic and/or very early post-HCT relapse. Prospective multi-center trials are planned to further evaluate lipo-cytara/dauno as a bridge to DLI/HCT in those with early relapse post-HCT and in those with refractory disease, with therapy to include CNS prophylaxis. Disclosures Stiff: Gilead/Kite Pharma: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Gamida-Cell: Research Funding; Incyte: Research Funding; Cellectar: Research Funding; Unum: Research Funding. Tsai:Jazz pharmaceuticals: Speakers Bureau; Jazz pharmaceuticals: Consultancy.

Introduction Most children with acute myeloid leukaemia (AML) harbour fusion genes which are ideal targets for molecular minimal residual disease (MRD) monitoring. However, evidence of prognostic significance is currently lacking and consequently most current paediatric AML treatment protocols rely on flow cytometric (FCM) evaluation to allocate treatment. Molecular MRD techniques provide significantly greater sensitivity and specificity and could allow more accurate outcome prediction, and consequently more personalised therapy, which is highly relevant in a disease where treatment related mortality, morbidity and relapse remain significant. Methods Between June 2016 and February 2019, MyeChild01 enrolled 170 children aged 0-18y with newly diagnosed AML who were randomly assigned to induction therapy with liposomal daunorubicin or mitoxantrone with cytarabine with or without gemtuzumab ozogamicin. Consolidation treatment was determined by karyotype, mutational profile and MRD status. Comprehensive centralised diagnostic assessment consisted of: Karyotype and fluorescence in-situ hybridisation (FISH) using a custom panel of probes to detect paediatric AML-associated gene fusions.PCR based screening for mutations in FLT3, NPM1 and CEPBA.Targeted capture of known fusion loci and paired end sequencing.RNA-seq using the Illumina TruSight fusion panel. Where a fusion gene was identified, RT-qPCR assays were designed and optimised for each patient. NPM1 mutation was also used as an MRD target if present. Paired PB and BM samples were requested after each cycle of treatment. Patients could have sequential monitoring after completion of therapy although this was not mandated. For this analysis, patients with core-binding factor (CBF) leukaemias i.e. inv(16)(p13q22) or t(8;21)(q22q22) with transcript levels above previously defined thresholds (Yin et al, 2012) were considered MRD positive. For all other targets, amplification in at least 2/3 replicates at For patients with CBF or NPM1 mutation, both molecular and FCM MRD status contributed to treatment allocation. Otherwise, FCM MRD was used unless there was no FCM target. Allogeneic stem cell transplantation (HSCT) was recommended for all patients with poor risk cytogenetics, those with intermediate risk cytogenetics who were MRD positive after cycle 2, and those with favourable risk cytogenetics who were MRD positive at the end of cycle 3. After completion of treatment, no specific advice was given regarding management of positive MRD results. Results We identified fusion genes in 126/170 patients (74%). We designed 55 unique RT-qPCR assays to specifically amplify 27 fusions with calculated sensitivity between 1:104 and 1:106. 62/126 children provided a complete set of samples: 31 (60%) with favourable, 18 (29%) with intermediate and 13 (21%) with high risk cytogenetic / molecular profiles. We analysed the effect of molecular MRD status at the end of protocol specified treatment, which included SCT in 17/62 (27%). One year event-free survival from diagnosis was 70% (95% confidence interval 52-82%) in patients who tested MRD negative compared to 11% (1-39%) in patients who tested MRD positive at the end of treatment (p Four patients received non-protocol specified SCT due to physician / family preference based on persistently positive or serially rising transcript levels after completion of treatment. At last follow up 4/4 were alive in complete remission. Rising transcript levels were observed in a further 8 patients to whom no pre-emptive treatment was given due to individual preference or lack of appropriate therapy. Haematological relapse subsequently occurred in 8/8. Conclusion Molecular MRD monitoring is feasible in the majority of children with AML, permitting refinement of response-adapted therapy. Molecular MRD status at the end of treatment is highly predictive of outcome, identifying molecular complete remission as a treatment goal for these children. Serially rising MRD levels reliably predict relapse in the absence of therapeutic intervention. Disclosures Dillon: Abbvie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; TEVA: Consultancy, Honoraria. Vyas:Astellas: Speakers Bureau; Abbvie: Speakers Bureau; Forty Seven, Inc.: Research Funding; Celgene: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Pfizer: Speakers Bureau; Daiichi Sankyo: Speakers Bureau. Amrolia:UCLB: Patents & Royalties. Baruchel:Bellicum: Consultancy; Servier: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria.

Method: A query was generated to retrieve all cases treated with CPX-351 at Beaumont Health System. SPSS software was used to perform descriptive statistics. Results: We found 11 cases treated with CPX-351 from 2017 to 2019. Six patients were male and 5 females. The median age at diagnosis was 67. Eight patients were Caucasian, two African American and one Asian. The median body mass index (BMI) was 27.1 and median body surface area (BSA) was ! treated with CPX-351 after a diagnosis of AML-MRC and 4 patients (36.3%) with t-AML. The median hospital stay was 35 days. The median units of red blood cells transfusion during hospital stay were 9 units and the median number of transfused platelet units was 6. Only 2 patients (18.1%) achieved complete response (CR) and 2 patients (18.1%) achieved complete response with incomplete blood count recovery (CRi). Three patients developed allergic reactions presented as a rash, 2 patients had significant bleeding and all 11 patients developed neutropenic fever. Three patients died during induction therapy and 2 patients underwent allogeneic hematopoietic stem cell transplant. Six patients (54.5%) died within 90 days of starting induction therapy. Conclusion: t-AML and AML-MRC remain to have dismal prognosis. Our study highlights the high early mortality rate associated with induction therapy with CPX-351. The most common cause of death was refractory or relapsed leukemia. The high incidence of neutropenic fever was also more prevalent to what has been reported. Disclosures No relevant conflicts of interest to declare.