Mylotarg (gemtuzumab ozogamicin) / UCB, PDL, Pfizer - LARVOL DELTA

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

Efficacy and safety of salvage therapies in relapsed/refractory Acute Myeloid Leukemia: A systematic review and network meta-analysis (ASH 2025) - "For safety, Cytarabine showed the lowest incidence of AEs (SUCRA = 0.71), while Enasidenib demonstrated the best profile in reducing mortality (SUCRA = 0.87). This NMA highlights Gilteritinib as the most effective and safest salvage therapy for R/R AML, particularly in patients with FLT3-mutated disease. Gemtuzumab Ozogamicin, Apamistamab, and Enasidenib also showed favorable outcomes, depending on molecular profiles and clinical priorities. These findings underscore the importance of individualized therapy selection based on efficacy, safety, and molecular characteristics."

Retrospective data • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • FLT3

Distinguishing on-target efficacy and off-target toxicity with antibody drug conjugates (ADCs) on diseased and normal hematopoietic cells (ASH 2025) - "Therefore, many ADCs, for example Trastuzumab-vc-MMAE (Enhertu) targeting specific diseased proteins (HER-2) which are not present on hematopoietic cells, may still have hematopoietic liabilities. Although this value was significantly different to that of Mylotarg on normal marrow progenitors, off-target toxicity was demonstrated. These data suggest that clonal assays with primary normal and diseased bone marrow cells may provide insight as to relative potency of an ADC on a disease-specific target as well as potential off-target toxicity to normal hematopoietic progenitors."

Clinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Thrombocytopenia • CD33 • HER-2 • PTPRC

Comparative long-term cardiovascular and hematologic outcomes of gemtuzumab ozogamicin containing regimens versus idarubicin containing regimens in acute promyelocytic leukemia: A propensity-matched analysis of real-world multicenter data (ASH 2025) - "Conclusions In this real-world, propensity-matched analysis of APL patients, ATRA + GO was associated with significantly lower 5-year mortality and incidence of cardiac arrest but increased risks of DIC compared to ATRA + idarubicin. These findings highlight the importance of individualized risk-benefit assessment when selecting induction regimens for APL."

Clinical • Real-world • Real-world evidence • Acute Promyelocytic Leukemia • Asthma • Atrial Fibrillation • Congestive Heart Failure • Diabetes • Endocrine Disorders • Heart Failure • Hematological Malignancies • Hypertension • Immunology • Ischemic stroke • Leukemia • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • Thrombosis • CD33

Fratricide-resistant anti-CD7 CAR-T cells for relapsed/refractory Acute Myeloid Leukemia (ASH 2025) - "Pt#1 is a 19-year-old male with t(10; 17)(p15; q21) AML, relapsed 13 months after initial diagnosis, who failed second-line therapy including FLA, gemtuzumab-ozogamicin, Venetoclax, and progressed after bridging therapy with 5-Azacytidine/Venetoclax...Both patients received a single infusion of PCART7 (1x10 6 CAR-T cells/kg) following cyclophosphamide/fludarabine-based lymphodepletion...Conclusion This is the first demonstration that PCART7 may represent a valuable and feasible option for patients with r/r AML and high CD7 expression, offering the potential to achieve MRD-negative CR. The safety profile of the treatment is favorable and both T and NK cells CD7 negative can contribute to protect patients against infections."

CAR T-Cell Therapy • IO biomarker • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Respiratory Diseases • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • CD4 • CD8 • CRP

Myeloid sarcoma as a pancreatic cancer mimic: Refining the clinical differential of pancreatic masses (ASH 2025) - "The patient was initiated on hydroxyurea for initial leukoreduction. After receiving his bone marrow biopsy results with molecular characterization, he received induction therapy with gemtuzumab ozogamicin (3 mg/m 2 ) and a 7-day infusion of cytarabine (100 mg/m 2 /day) with 3 days of concurrent daunorubicin (60 mg/m 2 )...Adding IHC staining for CD43 and MPO can help reveal this diagnosis. Increased awareness and earlier diagnosis with intervention are critical to improved prognosis and reduced morbidity."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Hepatology • Immunology • Leukemia • Oncology • Pancreatic Cancer • Pancreatitis • Sarcoma • Solid Tumor • CD20 • CD33 • CD34 • CD38 • CD79A • KIT • PTPRC • SDC1 • SPN

Role of DNA damage sensing and TP53 function as modulators of sensitivity to calicheamicin-based antibody-drug conjugates (ADCs) for acute leukemia (ASH 2025) - "Better survival of some patients with the CD33 ADC, gemtuzumab ozogamicin (GO), and the CD22 ADC, inotuzumab ozogamicin (InO), validate these efforts, but these ADCs are ineffective in many others...CLM-induced cytotoxicity was assessed in vitro in the presence/absence of a Mouse Double Minute 2 homolog (MDM2) inhibitor (idasanutlin), Ataxia-Telangiectasia Mutated (ATM) inhibitor (AZD1390, lartesertib), Ataxia Telangiectasia and Rad3-related (ATR) inhibitor (ceralasertib), Checkpoint Kinase 1 and Checkpoint Kinase 1 (Chk1/Chk2) inhibitors (prexasertib, BML-277), and poly(ADP-ribose) polymerase (PARP) inhibitor (veliparib)... Our studies identify ATM, MDM2, and TP53 as key modulators of CLM-induced cytotoxicity in acute leukemia cells. These results support further evaluation of combination therapies with corresponding small molecule inhibitors (currently pursued in patients with other cancers) toward possible clinical testing as novel strategies to increase the efficacy..."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Ataxia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Immunology • Leukemia • Movement Disorders • Primary Immunodeficiency • CD22 • CD33 • CDKN1A • FBXW7 • TP53

ORM-1153: A CD123-targeting degrader antibody conjugate with GSPT1-degrading payload exhibits potent preclinical antitumor activity in Acute Myeloid Leukemia (ASH 2025) - "Treatment options for unfit patients withoutactionable mutations are more limited following first-line treatment with the venetoclax / HMA standard-of-care...Currently, there is only one approved ADC for AML therapy:gemtuzumab ozogamicin (GO)... ORM-1153 combines CD123 target specificity with GSPT1 degradation to deliver potent anti-AML activityand a favorable safety profile in preclinical models. These data indicate that ORM-1153 may represent aviable therapeutic agent for the treatment of AML, including TP53-mutant and CD123-positive subtypes,and warrants further investigation in clinical trials."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD123 • GSPT1 • IL3RA • TP53

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

Real-world evidence evaluation of the safety and efficacy of intensive chemotherapy with or without gemtuzumab ozogamicin (GO) in patients with newly diagnosed Acute Myeloid Leukemia (AML) and favorable or intermediate risk cytogenetics (ASH 2025) - "Introduction Gemtuzumab ozogamicin (GO) is approved for use in combination with cytarabine plusdaunorubicin (7+3) for the treatment of de novo acute myeloid leukemia (AML) with favorable orintermediate risk cytogenetics. The 2-yearRFS was 73% (95% CI, 60-87) and 69% (CI 95%, 58-81) with 7+3+GO and 7+3, respectively.ConclusionWithin key subgroups of AML (CBF, NPM1mut and INT), the use of GO did not result in significantimprovements in CRc, MRD negativity rates and survival outcomes in this retrospective study.VOD, liver enzymes elevation, and bleeding were more frequent with GO. Further research,including larger sample size is needed to identify pts who benefit from GO and to optimizeclinical outcomes."

Clinical • HEOR • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Hematological Malignancies • Hepatology • Leukemia • NPM1

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

Survival outcomes with the use of gemtuzumab-ozogamycin in patients with acute myeloid leukemia receiving intensive chemotherapy stratified by molecular risk category (ASH 2025) - "GO was used from 2021 onward with fractionated dosing (3g/m2 day 1, 4,and 7) in combination with 7+3 IC or cytarabine consolidation. These results support GO use in the ELN 2022 fav-risk group. More work is needed to moreprecisely define which patients may benefit from GO beyond risk group."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Hepatology • Leukemia • CD33 • DNMT3A • FLT3 • NPM1 • 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

Establishing contemporary benchmarks for Acute Myeloid Leukemia outcomes and measurable residual disease: Real-world data utilization from the ELN-david MRD international working group (ASH 2025) - "Across alltreatment groups, most patients were not treated on clinical trials (86%), targeted (gemtuzumab-ozogamicin, FLT3 or IDH inhibitors) treatment was given to 36%, and the majority underwent allogeneicstem cell transplantation (64%)...Of the non-intensively treated patients, mostreceived venetoclax-based therapy (62%).Response evaluations showed complete remission (CR), or CR with incomplete count recovery (CRi) or CRwith incomplete platelet recovery (CRp) in 80% of patients that were treated with intensive chemotherapyand in 54% of patients that received non-intensive treatment...A standardized database has been developed to allow future analyses of individualpatient data. It is anticipated that data will be updated regularly, giving the opportunity to constructsynthetic control cohorts, allowing longitudinal correlation between evolving MRD practices and AMLoutcomes, and serving as benchmark for contemporary experience."

Clinical • Real-world • Real-world evidence • Residual disease • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia

Evaluating the efficacy of montelukast in reducing the incidence and severity of monoclonal antibodies-associated infusion reactions (Phase II Study) (ASH 2025) - P2 | "Mean LDH was within normal limits (182 IU/L; range 99–451).A total of 198 MAB doses administered: Rituximab: 100(50.5%)Daratumumab: 42(21%)Obinutuzumab: 18(9%)Blinatumomab: 18(9%)Gemtuzumab: 14(7%)Elotuzumab: 6(3%)All patients received at least one cycle (Cycle 1), with rituximab being the most frequently used (21patients). Due to the low number of events, no significant associations wereidentified for reactions in Cycles 2–6.Compared to published registration trial data for the included MABs, adding MKA was associated with a43% risk reduction of infusion reactions (p < 0.001).Conclusion10 mg MKA added to the premedication of MAB infusion is well tolerated and significantly reduces therisk of MCAAEsPatients with a history of atopy or medication allergy are at high risk for infusion reactions during the firstcycle of therapy, even with MKA premedication. This subgroup may benefit from closer monitoring andfurther intervention strategies."

Clinical • P2 data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Cell Lymphoma • Burkitt Lymphoma • Chronic Lymphocytic Leukemia • CNS Disorders • Depression • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Immunology • Infectious Disease • Lymphoma • Marginal Zone Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Psychiatry

Initial results from a phase 2 study of cladribine, cytarabine, and granulocyte-colony stimulating factor with gemtuzumab ozogamicin (CLAG-GO) for the treatment of patients with relapsed/refractory acute myeloid leukemia (ASH 2025) - P2 | "CD33-PGx evaluation suggestedassociation with poor response in patients with low score, though sample size was limited. The pre-specified number of responses was met, and enrollment in the study continues, with an additional 20patients planned."

P2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Malignancies • Hepatology • Leukemia • Neutropenia • Thrombocytopenia

Chemotherapy-free treatment for children and adolescents with newly diagnosed acute promyelocytic leukemia (APL): Results of the prospective ICC-APL-02 study. (ASH 2025) - P2 | "Introduction: Treatment of acute promyelocytic leukemia (APL) has been revolutionized over the past twodecades by the Introduction of both all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), leading tothe use of chemotherapy-free protocols in standard-risk (SR) adult patients.In October 2019, a multicenter European pediatric trial from the International Consortium for Childhood(ICC) APL delivering a non-chemotherapy-based treatment for children with newly diagnosed SR and HighRisk (HR) APL was started [NCT04793919]. Here, we report the results of the second planned interimanalysis of the ICC-APL-02 study. ICC-APL-02 Study is an open-label prospective, non-randomized, multicenter trial for childrenand adolescents (up to the age of 18) with newly diagnosed APL delivering a risk-stratified treatment[according to the modified pediatric criteria (Testi, Blood 2018)] based on the use of ATRA and ATO, plusgemtuzumab ozogamicin (GO) only in HR patients.During..."

Clinical • Acute Promyelocytic Leukemia • Bone Marrow Transplantation • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Hematological Malignancies • Leukemia • FLT3

Fludarabine and cytarabine is not superior to high dose cytarabine as consolidation therapy in standard risk AML in children: Results from the international Phase III MyeChild01 trial (ASH 2025) - "360 patients were randomised to FLA or HD AraC as course 3 and 4 in consolidation from Jan-2017 to Oct-2022; 180 to each arm.MethodsAt diagnosis 97% patients were allocated mitoxantrone and cytarabine (MA) with 79% receiving 1 or 3doses of GO in course 1 (Gibson, Blood; 144, Suppl 1, 2024)...SR patients received a second course of MA followed by two courses of either HD Ara C (3g/m2 bd ondays 1, 3, 5) or FLA (Fludarabine 30 mg/m2 and cytarabine 2g/m2 on days 1-5) based on randomisation.Randomisation was stratified by age; diagnosis (AML, MDS, and IMS); disease type (de novo, secondary); number of gemtuzumab ozogamicin (GO) doses...The median time from the start of course 3 to course 4 was 38 days for HD AraCand 41 for FLA.ConclusionFLA is not superior to HD AraC as consolidation therapy in children with SR AML. Patients with IRgenetics, particularly those with a non-high risk KMT2A rearrangement had a worse outcome with FLA.High Dose AraC should remain standard of care..."

Clinical • P3 data • Acute Myelogenous Leukemia • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Malignancies • Infectious Disease • Myelodysplastic Syndrome • Sarcoma • Solid Tumor • KMT2A

Etoposide can be safely removed from induction chemotherapy without impacting survival for pediatric acute myeloid leukemia – a report from the Children's oncology group study AAML1831 (ASH 2025) - P3 | "Introduction:Cytarabine, daunorubicin and etoposide have been the standard backbone of induction chemotherapy inChildren's Oncology Group (COG) frontline trials for pediatric acute myeloid leukemia (AML)...The use of gemtuzumab ozogamicin (GO) in Induction 1 of AAML1831 but notAAML1031 may be a confounding variable, though we have previously shown in AAML0531 that GO doesnot influence EOI1 MRD.Two-year survival outcomes were compared between AAML1831 vs AAML0531 or AAML1031...The removal of etoposide from induction did not diminish EOI1 MRD response or negatively impact RR,DFS or OS in pediatric AML when compared to historical data. While this observation may be influencedby improved supportive care, greater availability of salvage regimens and HSCT for CR2, we believe thatthese findings could set a new precedent for DA/GO induction therapy as the standard of care treatmentfor pediatric AML given the preserved efficacy and potential to reduce long-term..."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Pediatrics • FLT3

FLAG/VEN as a frontline induction therapy for AML: A multi-centre experience of Anthracycline free approach from India (ASH 2025) - "RGCIRC/IRB-BHR/04/2023 dated 4th February 2023.Induction therapy: All patients received tumor lysis syndrome prophylaxis with intravenous hydrationand Tab Febuxostat...Fludarabine 30 mg/m2 IV once daily for 4 days, Cytarabine 1500 mg/m2 IV oncedaily for 4 days...Filgrastim (biosimilar) 5 mcg/kg s/c once daily from day −1 to ANC > 500 cells/ µL...Venetoclax was given as 50 mg for day 1 and2 followed by 100 mg once daily...CBF AML patientsin CR1 at day 28 in both arms received FLAG with Gemtuzumab Ozogamicin (GO) based consolidationtherapy for 4 cycles... Our results suggests that FLAG/VEN approach can decrease induction mortality rate whichis anywhere about 20-25 % in a lower middle-income country like India. FLAG/VEN achieves high CR ratesof 93% which is comparable to FLAG/IDA/VEN approach without added toxicity in the real-world scenario.This approach needs to be tested in a randomized controlled trial to establish it as a standard therapy forAML."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Pneumonia • Respiratory Diseases • Septic Shock • Tuberculosis • TP53

Differences in outcomes with intensive chemotherapy in AML patients according to mutational status – recent real-world results (ASH 2025) - "ELN favorable (fav) and intermediate (int) riskpatients received induction with 7+3 (+ midostaurin for FLT3-mutated pts, and gemtuzumab ozogamicinfor some favorable risk pts)...The OS and RFS for ELN2022 int risk patients treated with IC has improved in recent years and is nowapproaching that of fav risk pts, likely related to the high HSCT rate achievable in int risk patients. ELNadv risk patients continue to have inferior outcomes, even with transplant; however, within this group,RUNX1 mutated patients have a better outcome with IC followed by HSCT than those with other MR genemutations. Revised prognostic scoring systems should take into account this heterogeneity within the advrisk group, as well as more recent outcome data."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • FLT3 • NPM1 • RUNX1 • TP53

Fractionated gemtuzumab ozogamicin (GO) with high-dose cytarabine (HiDAC) based induction chemotherapy is safe and highly effective for newly diagnosed favorable risk AML. (ASH 2025) - "Since the most benefitwas seen with GO given on days 1, 4, and 7 (fractionated GO, GO3) in the context of 7+3, wesubsequently conducted a single-arm phase 2 clinical trial of cladribine, high-dose cytarabine (HiDAC), G-CSF, and mitoxantrone (CLAG-M) + GO3. Pts with favorable-risk AML and MDS/AML who received HiDAC-based inductionchemotherapy +GO3 had low early mortality, infrequent liver injury, high rates of CR, and excellentsurvival outcomes, confirming this therapeutic strategy is well-tolerated and highly effective for favorablerisk AML."

Acute Myelogenous Leukemia • Hepatology • Liver Failure • BCORL1 • CEBPA • FLT3 • NPM1 • PTPN11 • SRSF2

Impact of pre-transplant chemotherapy cycles on allogeneic hematopoietic cell transplant outcomes in pediatric acute myeloid leukemia (ASH 2025) - "The most recent COG phase III study in upfront AMLtherapy, AAML1831, recommended two cycles of induction cytarabine-based chemotherapy followed byat least one cycle of consolidative therapy prior to HCT for high-risk patients...There were no significantdifferences between the two cohorts in age, sex, race/ethnicity, Karnofsky/Lansky score, gemtuzumabexposure, donor type, stem cell source, conditioning approach (busulfan vs TBI), conditioning intensity(reduced vs myeloablative), or GVHD prophylaxis...Additional cycles of consolidation therapy for patientsprimarily already in a flow MRD-negative state after 2 cycles did not appear to increase TRM or reducerates of relapse. These results suggest that it may be appropriate to proceed to allogeneic HCT if in flow-MRD negative remission after 2 cycles of induction therapy without the potential toxicity of subsequentchemotherapy cycles."

Clinical • Pre-transplantation • Acute Myelogenous Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Pediatrics • Transplantation • KMT2A

Proteogenomic analysis of NPM1-mutated AML reveals clinical heterogeneity related to differentiation states and mitochondrial metabolism (ASH 2025) - P3 | "Only few studies have so far exploredproteomic and proteogenomic disease characteristics that furthermore contribute to AML pathogenesis. We conducted a large-scale proteomic analysis on bone marrow blasts from 284 patients withnewly diagnosed NPM1-mutated AML enrolled in the phase III AMLSG 09-09 trial [NCT00893399],comparing intensive chemotherapy plus all-trans retinoic acid with or without gemtuzumab ozogamicin.We quantified the expression of 7,223 proteins...This gradient was significantly associated with genetic alterations, particularly anenrichment of FLT3-ITD (adjusted p-value <0.001) in immature disease, and the absence of DNMT3A(adjusted p-value <0.001), NRAS (adjusted p-value 0.026) and PTPN11 (adjusted p-value <0.001)mutations.Immature AML strongly correlated with BCL2 protein expression (Spearman's rho = 0.7), consistent withprevious evidence of sensitivity to venetoclax, a clinically approved BCL2 inhibitor... In summary, our..."

Clinical • Genomic analysis • Heterogeneity • IO biomarker • Omic analysis • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • DNMT3A • FLT3 • NPM1 • NRAS • PTPN11

Optimization of induction chemotherapy in pediatric patients with Acute Myeloid Leukemia: Real-world evidence to support removal of etoposide from induction 1 (ASH 2025) - "Introduction: Induction chemotherapy for pediatric AML has historically used cytarabine, daunorubicinand etoposide (ADE)...This may be particularlytrue in the modern era in which therapeutic intensity can be achieved by adding gemtuzumab-ozogamycin (GO)...Relatedly, most patients treated onstudy for cycle 1, stayed on for cycle 2: ADE 84% and DA 94%.We conducted two sensitivity analyses: one limited to patients diagnosed after 2020 to account fortemporal differences in pediatric AML including expanded cytomolecular and improved MRD testing,enhanced supportive care (e.g. dexrazoxane) and additional salvage options, and one restricted topatients who received GO in induction 1... These real-world data convincingly demonstrate comparable outcomes with ADE and DAwhen used in induction 1, particularly in patients who receive GO. These data suggest that DA can besafely used as standard backbone chemotherapy for pediatric patients in this cycle, which may reduceetoposide-related..."

Clinical • HEOR • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Pediatrics