Vyxeos (cytarabine/daunorubicin liposomal formulation) / Jazz, Nippon Shinyaku - LARVOL DELTA

A Phase 2 Trial of CPX-351 Combined With Venetoclax in Relapsed or Refractory Acute Myeloid Leukemia. (PubMed, Am J Hematol) - P2 | "CPX + VEN has activity in RR AML, particularly when used in first salvage and in patients who do not harbor TP53 mutations. ClinicalTrials.gov Identifier: NCT03629171."

Journal • P2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • TP53

Results from paradigm - a phase 2 randomized multi-center study comparing azacitidine and venetoclax to conventional induction chemotherapy for newly diagnosed fit adults with acute myeloid leukemia (ASH 2025) - "The study has met its primary endpoint. Aza-ven was associated with significantly improved EFS, as wellas higher rates of OR and CCR, vs IC in younger, IC-eligible pts. Overall survival data continue to mature."

Clinical • P2 data • Acute Myelogenous Leukemia • CNS Disorders • Depression • Hematological Malignancies • Infectious Disease • Leukemia • Psychiatry • Respiratory Diseases • Septic Shock • FLT3 • IDH1 • IDH2 • NPM1 • TP53

V-FAST Master Trial: Subgroup Analysis of Outcomes with CPX-351 Plus Midostaurin in Adults with Newly Diagnosed Acute Myeloid Leukemia By FLT3 Mutation Type (ASH 2022) - P1b | "V-FAST (Vyxeos – First Phase Assessment with Targeted Agents) is an open-label, multicenter, multi-arm, nonrandomized, phase 1b master trial (NCT04075747) to evaluate the safety and preliminary efficacy of CPX-351 combined with targeted agents (MID, venetoclax, enasidenib)...In conclusion, preliminary results from the V-FAST trial suggest the combination of CPX-351 + MID is feasible with a manageable safety profile and promising remission rates in adults with newly diagnosed, FLT3-mutated AML. Although conclusions are limited by the small numbers of patients in each subgroup, results are generally consistent for patients with FLT3 ITD and TKD mutations."

Clinical • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Leukopenia • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia • Transplantation • FLT3

Safety and Efficacy of Combining Midostaurin and Gemtuzumab Ozogamicin with Induction Chemotherapy in FLT3 mutated AML. (PubMed, Blood Adv) - "We evaluated the safety and efficacy of the combination of daunorubicin, cytarabine (DA), gemtuzumab ozogamicin (GO) and midostaurin (DAGO+m) for younger patients with newly diagnosed FLT3mut AML in the UK NCRI AML19 trial...DAGO2+m will now be evaluated in a randomised study (OPTIMISE-FLT3, ISRCTN 34016918). Trial: ISRCTN78449203."

Journal • Acute Myelogenous Leukemia • Transplantation • FLT3 • NPM1

HYPOMETHYLATING AGENTS PLUS VENETOCLAX VS INTENSIVE CHEMOTHERAPY PRIOR TO TRANSPLANT IN HIGH-RISK ACUTE MYELOID LEUKEMIA (EBMT 2026) - "The less-intensive regimen combining the hypomethylating agent (HMA) azacitidine (AZA) and the BCL-2 inhibitor venetoclax (VEN) has changed the treatment paradigm for older subjects with newly-diagnosed AML... Our study provides evidence supporting the use of HMA-VEN as an alternative, less toxic remission induction strategy for patients with ELN-2022 adverse-risk AML who are intended to proceed to allo-SCT"

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Transplantation • TP53

SEQUENTIAL CONDITIONING USING INDUCTION WITH CPX-351 FOLLOWED BY DOSE REDUCED CONDITIONING BEFORE ALLOGENEIC STEM CELL TRANSPLANTATION FOR HIGH-RISK ACUTE MYELOID LEUKEMIA (EBMT 2026) - "Dose-reduced conditioning regimens consisted of Thiotepa, Busulfan and Fludarabin (Flud) (n=8), Treosulfan and Flud (n=4), or Melphalan, BCNU and Flud (n=1)...GVHD prophylaxis included a calcineurin inhibitor and MMF in all pts, with 5 pts receiving additional ATG, 2 pts additional everolimus/sirolimus, and 5 pts additional ptCy... Sequential conditioning combining CPX-351 with dose-reduced conditioning regimen leads to promising outcome in 1st alloSCT for high-risk AML, but requires further evaluation within randomized clinical trials."

Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Biliary Cancer • Bone Marrow Transplantation • Cholangiocarcinoma • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Solid Tumor • Transplantation

A Phase II Study of Combination Daunorubicin, Cytarabine (Ara-c) and Nilotinib (TAsigna) (DATA) in Patients Newly Diagnosed with Acute Myeloid Leukemia with KIT Expression. (PubMed, Am J Hematol) - "Only one patient (3%) died in induction due to liver failure, which was thought secondary to daunorubicin. Our current study reveals good outcomes in patients who received HCT and may warrant a larger study to confirm our findings in that specific population."

Journal • P2 data • Acute Myelogenous Leukemia • Cardiovascular • Febrile Neutropenia • Hematological Malignancies • Hepatology • Hypertension • Liver Failure • Neutropenia • Renal Disease • Transplantation • KIT

CPX-351 in Down syndrome-associated Myeloid Leukemia: Results and Prognostic Factors from the Phase 3 ML-DS 2018 Trial. (PubMed, Blood) - P3 | "Intensity-reduced induction and reinduction therapy with cytarabine, idarubicin ± etoposide of the ML-DS 2006 trial was replaced with CPX-351 (66 U/m² on three days in course 1 and two days in course 2)...In conclusion, replacing intensity-reduced induction therapy with CPX-351 in ML-DS resulted in significantly lower event-free survival, highlighting the need for dose optimization to balance efficacy and toxicity in this sensitive patient population. EudraCT: 2018-002988-25."

Biomarker • Journal • P3 data • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Oncology • GATA1

CPX-351 versus venetoclax plus hypomethylating agents for newly diagnosed acute myeloid leukemia: A systematic review and meta-analysis. (PubMed, Leuk Res) - "CPX-351 demonstrated superior overall survival (OS) compared to 7 + 3 chemotherapy, while venetoclax and azacitidine significantly improved OS and composite remission rate compared to azacitidine alone...In conclusion, CPX-351 did not demonstrate superiority over Ven/HMA in composite remission rate and OS. Both regimens remain reasonable therapeutic options for older, newly diagnosed AML patients, and prospective comparative studies are needed to better guide treatment selection."

Journal • Retrospective data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Mitoxantrone liposome, subcutaneous cytarabine and G-CSF (CMG) combined with venetoclax as first-line treatment in secondary Acute Myeloid Leukemia (sAML) or elderly AML patients: A multicenter, prospective, single-arm clinical trial with concurrent control (ASH 2025) - P=N/A | "CMG+VEN represents a more safe alternative regimen in sAML and elderly AML patients,showing higher MRD negative rate and deserving further investigation."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm

Outcomes after Transplant in Relapsed/Refractory KMT2Ar (MLLr) and mNPM1 (NPM1c) leukemia Patients Achieving Remissions after Menin Inhibition: SNDX-5613 (revumenib) Ph1 Experience (ASH 2022) - P1/2 | "1 was among the 12 patients described in Table 1: a 40 yo F with KMT2Ar AML with FLT3 TKD, and 3 prior lines of therapy including 7+3+midostaurin and HSCT...She then had a molecular relapse and received CPX-351, gemtuzumab, venetoclax, and azacytidine, a 3rd allo-HSCT, and due to persistent positive MRD by flow, she received a donor lymphocyte infusion... In SNDX-5613 patients proceeding to transplant, durable remissions occurred across a range of heavily pre-treated patients. In addition to patients achieving CR/CRh, two patients with CRp also had ongoing remissions post-transplant. AUGMENT-101 continues to enroll patients, agnostic of transplant eligibility, with the option for SNDX-5613 post-transplant maintenance."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Septic Shock • Transplantation • FLT3 • KMT2A • NPM1

Lower-intensity CPX-351 plus venetoclax induction for adults with newly diagnosed AML unfit for intensive chemotherapy. (PubMed, Blood Adv) - P1b | "This study highlights that lower-intensity therapy of CPX-351 plus venetoclax as induction therapy provides a well-tolerated treatment option in adults with AML deemed unfit for intensive chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT04038437."

IO biomarker • Journal • Acute Myelogenous Leukemia • B Cell Non-Hodgkin Lymphoma • Hematological Disorders • Leukemia • Lymphoma • Oncology • TP53

CPX-351 Selectively Benefits Patients with AML and Myelodysplasia-Related Mutations in the Pivotal Randomized Trial. (PubMed, Blood Adv) - P3 | "The OS benefit of CPX-351 observed in the trial was driven by AML-MR with no benefit of CPX-351 in TP53-AML, where the primary prognostic factor was allelic state. Clinical Trial Information: NCT01696084."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • DDX41 • TP53

Molecular Features, Treatments and Outcomes for Pediatric AML Patients from APAL2020SC Pediatric Acute Leukemia (PedAL) Screening Trial (ASH 2024) - P1/2 | "The most common regimens were combinations including fludarabine/cytarabine (FLA); 18/40 (45%) and 12/18 (67%) achieved remission...In the prAML group, 10 of 23 with cycle 1 treatment and response data achieved remission : 2 with a FLA regimen, 5 with a venetoclax regimen, and 3 with CPX-351. Conclusion The APAL2020SC protocol is collecting valuable real-world treatment and response data, as well as comprehensive molecular characterization, for children with relapsed and refractory AML. These data will fill gaps in knowledge regarding this patient population and will inform the design of future therapeutic trials."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • AFDN • CBFA2T3 • FLT3 • GLIS2 • KMT2A • KRAS • MLLT10 • MLLT3 • NRAS • NSD1 • NUP98 • PTPN11 • RUNX1 • RUNX1T1 • WT1

CPX-351: From preclinical studies to future directions. (PubMed, Curr Opin Pharmacol) - "In this review, we analyze the path from preclinical studies to drug registration. Recent research highlights intestinal and heart toxicity of the drug, as well as current and potential future uses for CPX-351."

Journal • Preclinical • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Lower-intensity CPX-351 + venetoclax for patients with newly diagnosed AML who are unfit for intensive chemotherapy. (ASCO 2022) - P1b | "Lower-intensity CPX-351 + VEN was generally well tolerated in adults with newly diagnosed AML who are unfit for IC and showed promising initial efficacy, with CR or CRi in the majority of pts."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Cardiovascular • Cough • Infectious Disease • Myelodysplastic Syndrome • Myocardial Infarction • Pulmonary Disease • Respiratory Diseases • TP53

RISK STRATIFICATION OF NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA TREATED WITH VENETOCLAX IN COMBINATION WITH INTENSIVE CHEMOTHERAPY (EHA 2025) - P1/2, P2 | "While IC+VEN may abrogate certain ELN22 adverse features, pts with TP53mut and MECOMr still do poorly and require novel therapies. These findings require independent validation."

Combination therapy • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • IDH1 • IDH2 • KMT2A • KRAS • NRAS • PTPN11 • TP53

Combination of CPX-351 and Gemtuzumab Ozogamicin (GO) in Relapsed Refractory (R/R) Acute Myeloid Leukemia and Post Hypomethylating Agent (HMA) Failure High-Risk Myelodysplastic Syndrome (HR-MDS) (ASH 2024) - P2 | "Background : Outcomes of patients (pts) with HR-MDS or AML who are refractory to or progress after HMA ± Venetoclax (Ven) based therapy is dismal, warranting evaluation of newer agents...OS was meaningful in responders, considering multiple prior lines of therapy. Infection related events were the most common serious adverse events."

Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Neutropenia • Oncology • Pediatrics • Pneumonia • Respiratory Diseases • Septic Shock • CD33 • KMT2A • MECOM • TP53

Updated Results of CPX-351 in Combination with Gemtuzumab Ozogamicin (GO) in Relapsed Refractory (R/R) Acute Myeloid Leukemia (AML) and Post-Hypomethylating Agent (Post-HMA) Failure High-Risk Myelodysplastic Syndrome (HR-MDS) (ASH 2022) - P2 | "Background: Treatment outcomes in patients (pts) with AML and HR-MDS who progress after HMA +/- venetoclax (VEN) based regimen remains poor and warrants new therapeutic strategies... In a cohort composed predominantly of heavily pre-treated and VEN exposed adverse risk AML and HR-MDS pts, CPX-GO led to overall response (CR/CRh/MLFS/PR) rates of 52% and year-long median survival in responders (CR/CRh/MLFS) with no major non-hematological adverse event."

Combination therapy • Acute Myelogenous Leukemia • Bone Marrow Transplantation • CNS Disorders • Epilepsy • Hematological Malignancies • Infectious Disease • Mucositis • Myelodysplastic Syndrome • Transplantation • CD33 • NPM1

Incidence and Characteristics of Perianal Infections in CPX-351-Treated AML Patients. (PubMed, Cancers (Basel)) - "While the outcomes were favorable, PIs led to prolonged hospitalization. Routine rectal swab surveillance could be a valuable tool for risk stratification and preemptive strategies."

Journal • Acute Myelogenous Leukemia • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Mucositis • Oncology • Pain • Pneumonia • Septic Shock

Impact of Cytogenetics, Induction Chemotherapy and MRD on Outcomes of Intensively Treated AML with KMT2A Rearrangements – Experience from UK NCRI AML17 and AML19 (ASH 2024) - "Menin inhibitors have shown encouraging activity in relapsed/refractory disease, and trials combining these agents with intensive chemotherapy or venetoclax-azacitidine are ongoing...We also show that molecular MRD after course 2 is a strong predictor of long-term survival. These data are important to inform the design of future trials incorporating menin inhibitors in front-line therapy, and suggest that intensified induction and RT-qPCR MRD should be incorporated into these studies."

Acute Myelogenous Leukemia • Hematological Malignancies • FLT3 • KMT2A • MLLT3

Lower-Intensity CPX-351 + Venetoclax for Patients with Newly Diagnosed Acute Myeloid Leukemia Who Are Unfit for Intensive Chemotherapy: Post Hoc Analysis By Disease Risk Subgroups (ASH 2022) - P1b | "The combination of lower-intensity CPX-351 + VEN demonstrated efficacy in both the favorable/intermediate and poor disease risk subgroups, without excessive myelosuppression. These data also provide further insights into outcomes on CPX-351 combination therapies for the treatment of AML."

Clinical • IO biomarker • Retrospective data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia • TP53

A Randomized Comparison of CPX-351 and FLAG-Ida in Patients with High-Risk Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS) and MDS-Related Gene Mutations: A Subgroup Analysis of the UK NCRI AML19 Trial (ASH 2024) - "FLAG-Ida consisted of fludarabine 30 mg/m2 and cytarabine 2 g/m2 on days 2-6 (reduced to 1 g/m2 in patients >60 years), lenograstim 263 µg on days 1-7, and idarubicin 8 mg/m2 on days 4-6; consolidation regimens were MACE-MiDAC...A more favorable toxicity profile may have resulted in higher number of patients in CPX-351 arm getting to transplant. Post-transplant OS was longer with CPX-351 compared with FLAG-Ida."

Clinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Septic Shock • Thrombocytopenia • ASXL1 • BCOR • RUNX1 • SF3B1 • SRSF2 • STAG2 • TP53 • U2AF1 • ZRSR2

CPX-351 vs. conventional chemotherapy cardiotoxicity in high-risk AML: a post hoc phase III trial analysis. (PubMed, Cardiooncology) - "No CPX‑351-treated patients evaluated at final follow-up (follow-up 2) had decreased LVEF < 53% at follow-up 2, compared to 17.8% of 7 + 3-treated patients. The frequency of reported cardiac AEs was similar with CPX-351 (40.4%) and 7 + 3 (42.2%); most frequent were tachycardia in CPX-351-treated patients (CPX-351, 21.1%; 7 + 3, 8.9%) and atrial fibrillation/flutter in 7 + 3-treated patients (CPX-351, 7.0%; 7 + 3, 11.1%).  In addition to improving overall survival as demonstrated in the pivotal trial, CPX-351 may also be associated with less cardiotoxicity than 7 + 3 in high-risk AML patients."

Journal • P3 data • Retrospective data • Acute Myelogenous Leukemia • Atrial Fibrillation • Cardiovascular • Hematological Malignancies • Leukemia • Oncology

AML-MR Mutations Drive the Benefit of CPX-351 over 7+3 in the Pivotal Phase 3 AML Trial (ASH 2024) - P3 | "In this high-risk AML cohort, 5% had a germline DDX41 mutation with 100% CR and prolonged survival. Our results indicate that the benefit of CPX-351 over 7+3 is driven by the presence of AML-MR defining mutations."

P3 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • ASXL1 • BCOR • DDX41 • SF3B1 • SRSF2 • STAG2 • TP53 • U2AF1 • ZRSR2