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

Trials in progress: Phase IB/II of CPX-351 as maintenance therapy in AML patients ineligible for bone marrow transplantation (ASH 2025) - "In patients ineligible for allogenic hematopoietic stem cell transplant (HSCT), oral azacitidine is the only FDA approved treatment option...Eligible patients are newly diagnosed with AML in CR that have received any induction regimen with standard consolidation or a hypomethylating agent (HMA) and venetoclax, for at least 6 cycles and no more than 12 cycles...Prior HSCT patients are excluded, as well as cumulative lifetime anthracycline (doxorubicin equivalent) dose equal to or greater than 345 mg/m2, and for patients with prior mediastinal radiation therapy, anthracycline dose equal to or greater than 295 mg/m2...This investigator-sponsored study was supported by a research grant and provision of study drug from Jazz Pharmaceuticals. The study was independently designed and conducted by the investigators."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Transplantation

Update AML: Updated disease monitoring and treatment to enhance outcomes for pediatric AML (NCT07059975) (ASH 2025) - P1 | "These patients will receive the common salvage regimen Idarubicin-fludarabine-cytarabine (IdaFLA) as the second cycle (Induction 2) in lieu of standard DA8 (Daunorubicin-Cytarabine) chemotherapy...In UPDATE AML, IR patients will receive VIA in place of MA (mitoxantrone-cytarabine) to eliminate exposure to the cardiotoxic agent mitoxantrone. HR patients will receive VIA as Intensification 1 prior to SCT, in place of the genotoxic agent etoposide and to provide venetoclax exposure prior to SCT...All newly diagnosed patients at TXCH >1 month to <30 years old with non-FLT3-ITD+ AML will be eligible for enrollment after completing standard Induction 1 chemotherapy consisting of combination of daunorubicin and cytarabine +/- gemtuzumab...Over 3 years, the study is anticipated to accrue 36-40 patients and generate important feasibility data for our treatment and molecular MRD innovations. Our results will inform future cooperative group trials with respect to..."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Pediatrics • FLT3

Molecular response of Acute Myeloid Leukemia to induction with CPX-351 and its impact on prognosis (ASH 2025) - "Our data demonstrates that molecular response assessment is feasible in a real-world setting after AML induction therapy with CPX-351. CPX-351 induces CMR or VGPMR in 24% and PMR in 33%, resulting in molecular responses in 57% of pts. While conventional cytomorphology demonstrates a CR in 78% of pts., molecular analysis improves detection of residual disease."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • MECOM • RUNX1 • TET2 • TP53

Blast clearance dynamics and time to response across IDH1- and IDH2-mutated AML (ASH 2025) - "Also, no significant differences were found between IDH1 - and IDH2 -mutated patients in terms of response kinetics or overall survival. Together, these findings highlight potential biological differences among IDH mutation subtypes that may impact treatment response and require further investigation in larger prospective cohorts."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • IDH1 • IDH2

Impact of induction regimen and co-mutations on outcomes in AML with myelodysplasia-related changes (ASH 2025) - "Induction therapies were grouped into 4:1- Cytarabine plus anthracycline (7+3) with or without targeted therapy; 2-Hypomethylating agent (HMA) plus venetoclax with or without targeted therapy; 3-Cladribine- or fludarabine-based regimens; 4-Low-dose cytarabine with or without HMA or other targeted therapies... Epigenetic mutations are highly enriched in AML-MRC. CLIA-Ven achieved the highest CR/CRi rates, followed by Vyxeos, 7+3, and HMA-Ven. However, after adjusting for age, gender, and performance status, no differences were observed in RFS or OS among 7+3, HMA-Ven, or Vyxeos."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • ASXL1 • BCOR • CALR • CEBPA • DNMT3A • FLT3 • IDH1 • IDH2 • KRAS • NPM1 • NRAS • PTPN11 • RUNX1 • SF3B1 • SRSF2 • TET2 • TP53 • U2AF1

Real-world comprehensive single-institution analysis of AML with TP53-mutation (ASH 2025) - "For younger/fit patients (pts), intensive induction therapy is often considered while hypomethylating agents (HMA's) with or without venetoclax remains the standard for older/unfit pts...Frontline treatment regimens were stratified by intensive induction therapy (IIT) including 7+3 with or without cladribine, CPX-351, or clofarabine, cytarabine, G-CSF (CLAG) with or without investigational therapies...AlloSCT was associated with improved OS outcomes, although a limited proportion of patients were able to proceed to alloSCT as consistent with previously published data. These findings underscore the urgent need to develop novel therapeutic strategies, prioritize clinical trial options, and optimize alloSCT selection and timing for patients with TP53m AML."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • TP53

CPX-351 versus venetoclax plus hypomethylating agents for newly diagnosed acute myeloid leukemia: A systematic review and meta-analysis (ASH 2025) - "Recently, CPX-351 demonstrated superior overall survival (OS) compared to standard 7+3 chemotherapy in older adults with secondary AML, while the combination of venetoclax and azacitidine has shown greater efficacy than azacitidine alone in older adults with AML...While OS appeared to favor CPX-351, the difference was not statistically significant and we could not reject the null hypothesis. These findings, especially the trend toward improved OS with CPX-351, underscore the need for further prospective studies to more clearly identify the optimal induction therapy for older adults with AML."

Retrospective data • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome

Outcomes with liposomal daunorubicin/cytarabine – a single-center experience (ASH 2025) - "Outcomes were poorest in patients with del(7q). These findings underscore the need for additional strategies to improve long-term disease control in this high-risk population."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • ASXL1 • BCOR • DNMT3A • FLT3 • IDH2 • NPM1 • NRAS • PTPN11 • RUNX1 • SRSF2 • TET2 • TP53

Evaluation of the maternal-fetal transfer of liposomal daunorubicin and cytarabine in an ex vivo human placenta perfusion model to inform Acute Myeloid Leukemia therapy (ASH 2025) - "Cytarabine concentrations will be measured with a validated HPLC assay method with UV detection at 275 nm. Placental transfer will be evaluated by computation of Transport Fraction (T)=C Fetal vein -C Fetal artery /C Maternal artery -C Fetal artery andClearance Index (Cl I )= antipyrine clearance /chemo drug clearance."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome

Phase I study of lower dose CPX-351 combined with venetoclax for patients with higher-risk myelodysplastic syndrome or chronic myelomonocytic leukemia after hypomethylating agents failure (ASH 2025) - P1 | "Maintenance therapy consisted of azacitidine 75mg/m² on days 1-5 and VEN on days 1-7... Lower-dose CPX-351 combined with VEN was well tolerated and demonstrated a high earlyresponse rate in this high-risk population, with a substantial number of pts undergoing allo-SCT.Enrollment is ongoing to further evaluate efficacy in a larger cohort."

Clinical • P1 data • Chronic Myelomonocytic Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Metabolic Disorders • Mucositis • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Nephrology • Neutropenia • Pneumonia • Renal Disease • Respiratory Diseases • Thrombocytopenia • TP53

Prognostic implications of commutational patterns in NPM1-mutated AML receiving intensive treatment. cetlam group study (ASH 2025) - "Furthermore, prognosis may have been improved by the addition of midostaurin (MIDO) totreatment in FLT3mut patients and gentuzumab ozogamizine (GO) in FLT3wt patients... In this study, in patientswith NPM1mut AML treated with IC +/- MIDO or GO, the comutations analyzed were not associated withOS or DFS. However, mutations in DNMT3A and TET2 showed a tendency to be associated with a lowerlikelihood of CR. Age and functional status at diagnosis were confirmed as."

Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Infectious Disease • Leukemia • DNMT3A • FLT3 • IDH1 • IDH2 • NPM1 • PTPN11 • RAD21 • TET2 • TP53

Balancing the treatment outcomes: Survival and quality of life among older adults with AML (ASH 2025) - "In addition, a major breakthrough in treating patients 75 and older emerged with thecombination of azacitidine and venetoclax... Evaluating QOL and survival can improve understanding of the patient's journey withdifferent treatment intensities for older adults with AML. Baseline QOL was similar between groups. OnDay 30, the intensive group had better QOL in terms of fatigue and global distress, and this persisted atDay 60, with additional physical QOL differences between groups."

Clinical • HEOR • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia

Treatments and outcomes of adult patients with TP53-mutated acute myeloid leukemia (AML) in the real-life –Report of the prospective french observational ALFA-PPP study. (ASH 2025) - P | "Secondary AML (OR, 0.88 [95%CI,0.45-1.70]; p=0.714) or t-AML (OR, 1.39 [95%CI, 0.82-2.34]; p=0.217) were not significantly associated withTP53 mutation status.In the TP53-mutated cohort, treatment decision was intensive in 37 (22%) (median age, 63 years [56-66]; including 17 CPX-351), less intensive in 106 (64%) (median age, 75 years [68-79]; 78 AZA-VEN, 10 AZA, 18unknown), and best supporting care in 16 (10%) patients, while the 5/6 remaining patients died beforetreatment decision...ConclusionThis prospective real-life AML patient cohort confirms that patients with TP53 mutations display distinctfeatures and face a nearly incurable disease course, even when intensively treated. In absence ofeffective therapies, the knowledge of TP53 status at diagnosis appears to influence the decision topursue less intensive treatment options."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • TP53

Treatment selection and functional outcomes in treatment-related acute myeloid leukemia (tAML) and AML with myelodysplasia-related changes (MRC): A multicenter prospective cohort study (ASH 2025) - "A total of 54% patients received low-intensity chemotherapy: azacitidine ordecitabine in combination with venetoclax (44%), and other (10%)... To our knowledge, this is the first multicenter prospective multidimensional characterizationof adults with newly diagnosed tAML and AML MRC. One-third of participants had impaired physicalfunction, as measured by ADL or IADL. Patients with impaired ADL/IADL were more likely to be treatedwith low-intensity vs."

Clinical • Acute Myelogenous Leukemia • CNS Disorders • Depression • Genetic Disorders • Hematological Malignancies • Leukemia • Metabolic Disorders • Mood Disorders • Myelodysplastic Syndrome • Obesity • Psychiatry • Solid Tumor

Mynerva-gimema AML1919 ameliorate Trial: EARLY intensification in FLT3-mutated ACUTE myeloid leukemia based on peripheral blast clearance (ASH 2025) - P3 | "Since 2017, novel agents have receivedapproval for frontline treatment of selected patient categories, changing the uniform management to atargeted diversification of therapeutic approaches: the incorporation of the FLT3 inhibitor Midostaurinfor FLT3-mutated patients, the use of CPX-351 for therapy-related AML and AML with myelodysplasia-related changes, the implementation of Gemtuzumab ozogamicin prominently in patients with favorable-risk cytogenetics...Between April 2020 and June 2025, 28 study sites adhered to the trial and 147 FLT3-mut ptswere enrolled so far. Based on the expected distribution of patients into PBC-high and PBC-low category,a total of 172 subject is to be recruited to include 86 PBC-low patients suitable for randomization to theconventional and experimental arm"

Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • FLT3

Daunorubicin and cytarabine liposomal (CPX-351) plus glasdegib for newly diagnosed secondary Acute Myeloid Leukemia: Results of University of California hematologic malignancies consortium trial 1913 (ASH 2025) - P2 | "Thus clearance, not just morphologic remission,may be a critical endpoint in sAML.Conclusion Despite encouraging safety/activity, the study did not meet the primary endpoint of EFS. TheCPX-351/glasdegib combination may offer benefit in sAML, particularly as a bridge to alloHCT.Encouraging responses with MRDneg rates were observed in TP53mut pts."

Acute Myelogenous Leukemia • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Neutropenia • Oncology • Respiratory Diseases • Septic Shock • TP53

Subclinical cardiac changes following CPX-351 induction in adults with favorable/intermediate-risk AML (ASH 2025) - "If lesser toxicity is shown, CPX-351 could potentially be preferred in patients withpreexisting cardiac dysfunction or elevated risk for heart failure, and may reduce the need forcardioprotective agents such as dexrazoxane. As with any recently introduced agent that may be used toreplace standard therapy, it is crucial to fully characterize any toxicity profile, including with long-termfollow-up. We previously conducted a pilot study of CPX-351 with or without gemtuzumab ozogamicin(GO) in 25 adults (age 15%, including one who met both criteria. These five patients(20%) represent the subset with significant cardiac changes.In this cohort, both EF and GLS reductions were already evident post-induction in patients with significantcardiac changes."

Clinical • Acute Myelogenous Leukemia • Alopecia • Congestive Heart Failure • Heart Failure • Immunology • Myelodysplastic Syndrome

Efficacy and safety of CPX-351 in high-risk Acute Myeloid Leukemia (ASH 2025) - "Our preliminary results support the previous evidence that CPX-351 improves overallsurvival in high-risk AML regardless of patients age and with acceptable safety profile."

Clinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Mucositis • Myelodysplastic Syndrome • TP53

Phase 1/1b dose escalation and expansion of CPX-351 in combination with gemtuzumab ozogamicin in newly diagnosed Acute Myeloid Leukemia (AML) (ASH 2025) - P1 | "In this dose escalation study, CPX-351 with GO induced high CR/CRi rate with nearly allresponding pts achieving MRD(-), including higher-risk ELN subsets. Safety and tolerability wereacceptable and Cohort A (Day 1 GO) was declared the recommended expansion dose with cytopeniaduration similar to CPX-351 monotherapy. Dose expansion focusing on pts with ELN int/adv risk isunderway."

Combination therapy • P1 data • Acute Myelogenous Leukemia • Anorexia • Febrile Neutropenia • Infectious Disease • Myelodysplastic Syndrome • Neutropenia • Septic Shock • Thrombocytopenia • ASXL1 • CD33 • CEBPA • DNMT3A • FLT3 • NRAS • RUNX1 • STAG2 • TET2 • TP53

Effectiveness and safety of CPX-351 in younger patients <60 years with newly diagnosed secondary Acute Myeloid Leukemia: Pooled analysis of US (V-RULES) and UK (CREST-UK) real-world studies (ASH 2025) - P=N/A | "Limitations of this studyinclude its retrospective nature with clinician selected treatment in major medical centers. Thisretrospective real-world pooled analysis of patients treated at 25 US and UK medical centersdemonstrates favorable effectiveness and acceptable tolerability of CPX-351 in younger adults with ND t-AML or AML-MRC eligible for intensive chemotherapy."

Real-world • Real-world evidence • Retrospective data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • TP53

VYSION (VYxeoS liposomal® Italian Observational study iN the real practice): Study design and baseline characteristics (ASH 2025) - P | "VYSION has the potential to provide valuable insights into effectiveness and safety of CPX-351in routine clinical practice. ClinicalTrials.gov ID: NCT06143839."

Clinical • Observational data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • TP53

Somatic mutations predict risk of invasive fungal disease in patients with acute myeloid leukemia treated with intensive induction chemotherapy (ASH 2025) - "In a cohort of patients not receiving antifungal prophylaxis, we show that integrating pre-treatment host characteristics, blood counts, and AML molecular data identifies patients at high risk ofIFD following IC. Mutations in TP53, SRSF2, and IDH1 may lead to qualitative or quantitative immunealterations that increase susceptibility to IFD upon IC induced myelosuppression. Our findings indicatethat these baseline risk factors identify vulnerable AML subgroups for whom a targeted approach toantifungal prophylaxis may be used."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Pulmonary Disease • Respiratory Diseases • IDH1 • NPM1 • SRSF2 • TP53

Measurable residual disease (MRD) assessment as an early end point oftreatment efficacy in acute myeloid leukemia (AML): A pethema studyof 2,623 patients (Pts) treated with intensive therapy (ASH 2025) - "Pts were mainlytreated with 3+7 (n=2,160), followed by 3+7 plus a FLT3 inhibitor (n=137), FLAG-based regimens (n=97).Additional treatments included CPX-351 (n=59), 3+7+Etoposide (n=44), 3+7+GO (n=37), and others (n=89).Pts were stratified into low (CBF, n=348), intermediate-low (CEBPA/NPM1+ and FLT3-, n=392),intermediate-high (MRC 2010 intermediate or normal karyotype with FLT3- and NPM1-, n=738) and high(MRC 2010 high or FLT3+, n=784) genetic risk... MRD assessment by MFC proved to be more sensitive than CR and showed a strong patient-level association with survival. MRD negative rates achieved with each treatment were also associatedwith differences in survival. While these results qualify MRD as a potential early end point of treatmentefficacy in AML pts considered fit for intensive therapy, attention should be paid to genetically-definedintermediate risk groups in whom MRD status may guide treatment decisions that could ameliorate thepoor prognosis of positive MRD."

Clinical • Residual disease • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • CEBPA • NPM1

Phase I/II clinical trial of bortezomib in combination with CPX-351 for the treatment of newly-diagnosed TP53-mutated Acute Myeloid Leukemia (NCT07008638) (ASH 2025) - P1/2 | "We treated TP53m AML samples with carfilzomib andbortezomib (BTZ)...APL and patients withextramedullary or CNS disease are excluded. The protocol is under IND 175618, and the first patient isexpected to be enrolled in August 2025."

Clinical • Combination therapy • P1/2 data • Acute Myelogenous Leukemia • CNS Disorders • Hematological Malignancies • Leukemia • TP53

Final results of a phase I/II trial of palbociclib and CPX-351 in patients with Acute Myeloid Leukemia (ASH 2025) - P1/2 | "Toxicities were consistent with those expected from CPX-351 and manageable with supportive care.ConclusionsThe combination of palbociclib and CPX-351 was safe and showed efficacy as frontline treatment fornewly diagnosed AML, including those with R/R AML and adverse risk features. These results support thecontinued evaluation of CDK4/6 inhibition as a combination strategy in AML."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Cerebral Hemorrhage • CNS Disorders • Febrile Neutropenia • Hematological Malignancies • Hypertension • Infectious Disease • Leukemia • Nephrology • Neutropenia • Respiratory Diseases • Septic Shock • Thrombocytopenia • FLT3 • IDH1 • TP53