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

VBP101: Allogeneic Engineered Hematopoietic Stem Cell Transplant (HCT) Lacking the CD33 Protein, and Post-HCT Treatment With Mylotarg, for Patients With CD33+ AML or MDS (clinicaltrials.gov) - P1/2 | N=67 | Terminated | Sponsor: Vor Biopharma | Trial completion date: Jan 2027 ➔ May 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Oct 2025 ➔ May 2025; Lack of Funding

Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • CD33 • HLA-B • HLA-C • HLA-DQB1 • HLA-DRB1

NCI-2018-01613: Fractionated Gemtuzumab Ozogamicin in Treating Measurable Residual Disease in Patients With Acute Myeloid Leukemia (clinicaltrials.gov) - P2 | N=36 | Recruiting | Sponsor: University of Washington | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33

Gemtuzumab ozogamicin in first-line treatment of CBF-AML: insights from a retrospective multi-center analysis. (PubMed, Leukemia) - "Despite delayed platelet recovery, high-grade toxicities were not increased in GO-treated patients. These findings support the integration of GO into treatment protocols for IC-eligible patients with CBF-AML."

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

Real-World Efficacy and Safety of Gemtuzumab Ozogamycin (GO) and 3 + 7 regimen in fit newly diagnosed Acute Myeloid Leukemia (AML) patients. A Retrospective multicenter study of "Rete Ematologica Pugliese" (REP). (PubMed, Leuk Res Rep) - "Between March 2020 and February 2023, 34 consecutive fit CD33+ AML patients, median age 54.5 years (range, 25-75) were treated. This study confirms the efficacy and toxicity data reported in clinical trials, highlighting the feasibility of GO based chemotherapy also in patients older than 60 years and as a bridge to allo-HSCT."

Clinical • Journal • Real-world evidence • Retrospective data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • CD33

Gemtuzumab ozogamicin in first-line treatment of CBF-AML: insights from a retrospective multi-center analysis (Leukemia, Nature) - "In this registry-based study, we evaluated the impact of adding GO to IC in 265 CBF-AML patients from the SAL, AMLCG, and CELL cooperative study groups. Patients receiving GO had a 2-year overall survival of 90% compared with 80% in those without GO (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.21–0.95, P = 0.036) and a 2-year event-free survival of 51% versus 36% (HR 0.69, 95% CI 0.48–0.99, P = 0.046). While complete remission rates in GO vs. non-GO patients were comparable (89% vs. 90%, P = 0.81), more GO patients achieved measurable residual disease-negative remission (77% vs. 49%, P < 0.001), resulting in numerically reduced cumulative incidence of relapse (HR 0.67, 95% CI 0.43–1.02, P = 0.06)."

Retrospective data • Acute Myelogenous Leukemia

Gemtuzumab ozogamicin in first-line treatment of CBF-AML: insights from a retrospective multi-center analysis (Leukemia, Nature) - "In this registry-based study, we evaluated the impact of adding GO to IC in 265 CBF-AML patients from the SAL, AMLCG, and CELL cooperative study groups. Patients receiving GO had a 2-year overall survival of 90% compared with 80% in those without GO (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.21–0.95, P = 0.036) and a 2-year event-free survival of 51% versus 36% (HR 0.69, 95% CI 0.48–0.99, P = 0.046). While complete remission rates in GO vs. non-GO patients were comparable (89% vs. 90%, P = 0.81), more GO patients achieved measurable residual disease-negative remission (77% vs. 49%, P < 0.001), resulting in numerically reduced cumulative incidence of relapse (HR 0.67, 95% CI 0.43–1.02, P = 0.06)."

Retrospective data • Acute Myelogenous Leukemia

Platform-based opportunities to streamline animal use in support of the 3Rs - recommendations from an antibody-drug conjugate analysis. (PubMed, Regul Toxicol Pharmacol) - "The field of antibody drug conjugates (ADCs) continues to be an active area of development which has greatly evolved over the past 25 years since the first approved ADC in 2000 (Mylotarg)...This realization contributed to the passage of the FDA Modernization Act 2.0 and the drafting of additional legislation (FDA Modernization Act 3.0) and the recent 'Roadmap to Reducing Animal Testing in Preclinical Safety Studies' which codify support in the US for the refinement of nonclinical toxicology programs and signal an opportunity for decreased reliance on animal models for safety evaluation. Similarly, the European Federation of Pharmaceutical Industries and Associations (EFPIA) recently released 'EFPIA Recommendations on Phasing Out Animal Testing for Chemical Safety Assessments' with comparable assessments and recommendations aimed at the evolution of pharmaceutical toxicity testing away from animal studies."

Journal • Gene Therapies • Infectious Disease • Novel Coronavirus Disease

Drug-induced sinusoidal obstruction syndrome: a real-world pharmacovigilance study based on the FDA Adverse Event Reporting System (FEARS). (PubMed, BMC Pharmacol Toxicol) - "Our study offers a potential list of drugs commonly associated with SOS and identified several novel drugs associated with SOS that had not been previously described in LiverTox®."

Adverse events • Journal • Real-world evidence

A Phase Ia/Ib Trial of Revumenib Combined With Cytarabine, Daunorubicin, and Gemtuzumab Ozogamicin (GO) in Frontline and Relapsed /Refractory Pediatric Acute Leukemia Patients (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P1 trial • Hematological Malignancies • Leukemia • Oncology • Pediatrics

Incidence of Clinically Significant Neutropenia and Complications Related to Antibody-Drug Conjugates: A Real-Word Study at University of California (MASCC-ISOO 2025) - "Methods A multi-center retrospective study utilized UC Health Data Warehouse records of patients receiving at least one dose of the ten most-used ADCs between January 2012 and August 2024: fam-trastuzumab deruxtecan, ado-trastuzumab emtansine, brentuximab vedotin, sacituzumab govitecan, enfortumab vedotin, gemtuzumab ozogamicin, inotuzumab ozogamicin, polatuzumab vedotin, belantamab mafodotin, and tisotumab vedotin. Patient distribution and primary outcomes Table 3. Secondary outcomes Conclusions The most commonly used ADCs in contemporary practice, such as fam-trastuzumab deruxtecan, and ado-trastuzumab emtansine, were associated with reasonably low rates of febrile neutropenia and related events."

Clinical • Anemia • Febrile Neutropenia • Neutropenia • Oncology

PREDICTORS FOR ANTIBODY-DRUG CONJUGATES (ADCS) ASSOCIATED CLINICALLY SIGNIFICANT NEUTROPENIA AT UNIVERSITY OF CALIFORNIA HOSPITALS (MASCC-ISOO 2025) - "The study focused on the ten most commonly used ADCs: fam-trastuzumab deruxtecan, ado-trastuzumab emtansine, brentuximab vedotin, sacituzumab govitecan, enfortumab vedotin, gemtuzumab ozogamicin, inotuzumab ozogamicin, polatuzumab vedotin, belantamab mafodotin, and tisotumab vedotin. Conclusions Selected ADCs are associated with significant risks of severe neutropenia. These findings highlight the importance of identifying patients who are predisposed to these adverse effects and implementing tailored management strategies."

Clinical • Anemia • Breast Cancer • Hepatology • Liver Failure • Neutropenia • Oncology

NCI-2019-01726: Gentuzumab Ozogamicin and Midostaurin Combination With Standard Cytarabine and Danunorubi Midostaurin as a Novel Approach to Treating Patients With Newly Diagnosed FLT-3 Mutated Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Uma Borate | Trial primary completion date: Jun 2025 ➔ Aug 2024

Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33 • FLT3

Targeting acute myeloid leukemia through antibody engineering: innovations in immunotherapy and combination regimens. (PubMed, Clin Exp Med) - "Key innovations include CD33-targeted gemtuzumab ozogamicin, CD123-directed bispecific engagers, and anti-CD47 agents that disrupt "don't eat me" signals...Clinical trials demonstrate promising results, including improved remission rates and survival in refractory/relapsed AML when combining antibodies with hypomethylating agents, venetoclax, or checkpoint inhibitors...Emerging strategies such as biomarker-driven personalization, TME modulation, and engineered NK-cell engagers are poised to address these limitations. By integrating preclinical insights with clinical data, this review underscores the potential of antibody-based combinatorial regimens to redefine AML therapy, offering durable responses and bridging the gap to curative approaches."

IO biomarker • Journal • Review • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD123 • CD33 • IL3RA

A CD33-DELETED ALLOGRAFT (TREM-CEL) ENABLES GEMTUZUMAB OZOGAMICIN MAINTENANCE POST-HEMATOPOIETIC CELL TRANSPLANT WITH THERAPEUTIC EXPOSURES AND LOW TOXICITY IN PATIENTS WITH ACUTE MYELOID LEUKEMIA (EHA 2025) - P1/2 | "Aims: Tremtelectogene empogeditemcel (trem-cel, formerly VOR33) is a hematopoietic stem and progenitor cell product produced by CRISPR/Cas9 gene-editing to delete CD33 from CD34+ cells allowing CD33-directed targeting of leukemia while sparing the donor graft...Donor CD34+ cells are isolated from G-CSF/plerixafor-mobilized peripheral blood...If patients relapse post-HCT, they may receive a fractionated induction dose of GO and/or are eligible to receive donor-derived CD33 CAR-T on the VBP301 trial (NCT05984199).25 patients received trem-cel with a median dose of 8.11x106 CD34+ cells/kg (2.62-12.44) and CD33 editing efficiency median 90% (71-94%)... Preliminary results from VBP101 show trem-cel rapidly engrafts, sustains hematopoiesis with persistent myeloid absence of CD33 and protects from prolonged deep GO-associated cytopenias. GO exposures correlate with higher doses seen in R/R AML patients, likely due to reduction CD33-mediated clearance and supports an..."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia • Transplantation • CD33 • CD34

VEN-BASED SCHEMES, ARE THEY BETTER THAN "3 + 7"? (EHA 2025) - "Hypomethylating agents (HMAs) in combination with venetoclax (HMA-Ven) have emerged as a less intensive alternative with promising efficacy and a more favorable safety profile. Aims: This study aimed to compare the efficacy and safety of "3+7" (+/- gemtuzumab ozagamicin or midostaurine) and HMA-Ven... HMA-Ven is non-inferior to "3+7" in terms of OS and PFS in AML, with a significantly lower incidence of FN and IFD. These findings suggest that HMA-Ven could be a preferred treatment option for AML, balancing efficacy with a better safety profile."

Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology

INTEGRATIVE SYSTEMS BIOLOGY APPROACH UTILIZING TRANSCRIPTOMIC AND MUTATIONAL PROFILES TO UNVEIL PROGNOSIS-ASSOCIATED MOLECULAR PATHWAYS IN ACUTE MYELOID LEUKEMIA (EHA 2025) - "Pathway Identification: The GNN models identified 94 prognosis-associated KEGG pathways, resolved these into 77 functionally coherent subnets (381 genes) with 15 subnets regulated by DNA methylation.Consensus Prognostic Model: 19 subnets formed a consensus Cox model achieving superior 5-year survival prediction (AUC: 0.85 vs. ELN2017's 0.73).Expression-Driven AML Subtyping: 2 SubNetclusters emerged: Cluster 1 (high-risk, fatty acid metabolism/lymphocyte infiltration) associated with adverse ELN2022 genetics (e.g,TP53 mutations), while Cluster 2 (low-risk, amino acid metabolism/monocyte infiltration) associated with favorable/intermediate risk(e.g,IDH1/2 mutations).Therapeutic Implications: Drug-gene mapping revealed 26 therapeutic targets across 19 subnets inside consensus Cox model, including 8 approved agents (e.g., Gemtuzumab ozogamicin targeting CHEK1) and prioritized tyrosine kinase inhibitors as particularly promising candidates... This study pioneers a..."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CHEK1 • FLT3 • IDH1 • IDH2 • NPM1 • TP53

DEFIBROTIDE TREATMENT OUTCOMES IN PATIENTS WITH VENO-OCCLUSIVE DISEASE/SINUSOIDAL OBSTRUCTION SYNDROME (VOD/SOS) OCCURRING AFTER EXPOSURE TO INOTUZUMAB (INO) OR GEMTUZUMAB (GO) (EHA 2025) - "InO/GO exposure was common among defibrotide-treated patients in the DEFIFrance and EBMT PASS registries, consistent with being a known risk factor for VOD/SOS. The VOD/SOS resolution rate, time to resolution, and defibrotide treatment duration appear similar in patients with or without InO/GO exposure, highlighting the importance of vigilant monitoring, prompt VOD/SOS diagnosis, and defibrotide treatment. The safety profile of defibrotide in this pooled analysis is consistent with previous studies."

Clinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Hematological Disorders • Hematological Malignancies • Hepatology • Infectious Disease • Leukemia • Oncology • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases • CD22 • CD33

ON- AND OFF-TRIAL EXPERIENCE SUPPORTS FRACTIONATED GEMTUZUMAB OZOGAMICIN WITH HIDAC-BASED INDUCTION CHEMOTHERAPY IS SAFE AND HIGHLY EFFECTIVE FOR NEWLY DIAGNOSED FAVORABLE RISK AML. (EHA 2025) - P1/2 | "Background: Multiple trials, including one at our institution, have shown fractionated gemtuzumab ozogamacin (GO) added to high-dose cytarabine (HiDAC)-based induction chemotherapy improves outcomes, and was therefore adopted as our standard treatment in 2022 for fit patients with favorable risk AML or MDS/AML...Of these, 21 were treated on a phase 2 trial evaluating GO3 + CLAG-M (mitoxantrone dose = 18mg/m2 x 3 days, NCT03531918), 90 received GO3 + CLAG-M as standard of care, and 23 received GO + FLAG-IDA... While some off-trial pts could be defined as 'ineligible' for induction therapy by TRM score, many were treated successfully with an intensified regimen and are experiencing prolonged survival. In this large cohort with favorable risk disease, we observed treatment with GO3+CLAG-M or FLAG-IDA led to frequency MRD- CR responses, while early mortality was uncommon. Off-trial pts with high TRM scores did worse, partially accounting for the on- vs off-..."

Acute Myelogenous Leukemia • Hematological Malignancies • Oncology

GEMTUZUMAB OZOGAMICIN AS FIRST LINE TREATMENT OF ACUTE MYELOID LEUKAEMIA (AML) WITH FAVOURABLE PROGNOSIS - A REAL LIFE NATIONAL EXPERIENCE FROM GRUPO PORTUGUÊS DE LEUCEMIAS AGUDAS (GLPA) (EHA 2025) - "13 pts received Ursodeoxycholic acid in addition to antifungal prophylaxis, after a significant increase in the hepatic enzymology, mostly after (I) (71-91% pts with elevated liver enzymes). In this analysis we demonstrate feasibility of including GO in first line AML treatment in a real world setting. In our intensively treated CBF and NPM1 AML pts, 87% achieved MRD negativity. With a median follow up of 14 months RFS and OS were favorable."

Clinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Hepatology • Infectious Disease • Leukemia • Liver Failure • Oncology • Thrombocytopenia • CD33 • NPM1

GO-FIRST: REAL-WORLD DATA OF FRONT LINE GEMTUZUMAB OZOGAMICIN IN INTERMEDIATE AND FAVORABLE RISK AML PATIENTS IN A MULTICENTER RETROSPECTIVE CHART REVIEW (EHA 2025) - "Pts with prior tx other than hydroxyurea for leukoreduction were excluded.Data of 84 pts were collected with a median observation time of 2.7 years...All pts received induction with GO and cytarabine together with daunorubicin (90.5%) or idarubicin (10.7%)... Pts treated with GO exhibited substantial event- and relapse-free survival, both exceeding data observed in the GO Phase III pivotal trial (not adjusted for differences between populations). Three doses of GO in induction were shown to be effective, and GO demonstrated effectiveness in the intermediate cytogenetic risk group; further analyses will explore outcomes among these intermediate-risk pts."

Real-world • Real-world evidence • Retrospective data • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Hepatology • Leukemia • Oncology • CD33

THE COMBINATION OF VENETOCLAX AND AZACITIDINE IS ASSOCIATED WITH A REDUCED RISK OF INFECTIOUS EVENTS COMPARED TO INTENSIVE CHEMOTHERAPY IN PATIENTS WITH RELAPSED/REFRACTORY AML. A RETROSPECTIVE STUDY BY THE FHU GOAL (EHA 2025) - "IC salvage therapy included cytarabine (n=156, 96%), anthracyclines (n=98, 60%), and gemtuzumab-ozogamicin (n=45, 28%). These results suggest that, without affecting leukemia control, VENAZA is associated with a reduction in the risk of infections, particularly severe (grade 3-5) infections, compared to IC in patients with R/R AML."

Retrospective data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • FLT3 • NPM1

PHASE 1/1B TRIAL OF TALAZOPARIB AND GEMTUZUMAB OZOGAMICIN IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY CD33+ ACUTE MYELOID LEUKEMIA (EHA 2025) - "19 (79%) had failed prior venetoclax (ven) and HMA, 1 prior IDH inhibitor, and 3 prior FLT3 inhibitor. This phase 1b study evaluated the safety, tolerability, and preliminary efficacy of Tala+GO in adult pts with CD33+ R/R AML. Most (79%) had failed prior ven. No DLT was reported."

Clinical • P1 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hepatology • Infectious Disease • Leukemia • Neutropenia • Oncology • Respiratory Diseases • Septic Shock • Solid Tumor • Thrombocytopenia • ASXL1 • BCOR • CD33 • DNMT3A • FLT3 • IDH1 • RUNX1 • SRSF2 • TET2

REAL-WORLD UTILIZATION, SAFETY, AND CLINICAL OUTCOMES WITH GEMTUZUMAB OZOGAMICIN (GO) IN COMBINATION WITH INTENSIVE CHEMOTHERAPY IN PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA (EHA 2025) - "The findings from this study suggest that GO in combination with 7+3 is effective in achieving and maintaining CRc in pts with favorable and intermediate risk AML, but carries risks of serious complications, including VOD and hemorrhage which can lead to death. Risk mitigation strategies are needed to decrease GO-related complications while maintaining its anti-leukemic efficacy."

Clinical • Clinical data • Combination therapy • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Cerebral Hemorrhage • CNS Disorders • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hepatology • Infectious Disease • Leukemia • Neutropenia • Oncology • Otorhinolaryngology • Pneumonia • Respiratory Diseases • Septic Shock • NPM1 • RUNX1 • RUNX1T1

IDENTIFICATION OF IMMUNE MODULATORS OF CAR-T CELLS TARGETING CD33 IN ACUTE MYELOID LEUKEMIA (EHA 2025) - "Treatment with the antibody-drug conjugate Gemtuzumab Ozogamicin (GO), directed against CD33 (Siglec-3), is approved in relapsed/refractory AML... This study seeks to uncover novel immune regulators that influence CD33 CAR-T cell function and persistence in AML. By leveraging a comprehensive CRISPR screen and rigorous validation approaches, we aim to identify targets that enhance CAR-T cell efficacy, persistence, and resistance to antigen-driven exhaustion. The findings will provide critical insights into optimizing CAR-T therapy for AML and may contribute to the development of next-generation immunotherapies with improved clinical outcomes."

CAR T-Cell Therapy • IO biomarker • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33 • CD4

Pharmacovigilance insights into antibody-drug conjugates: a multi-database analysis of adverse events in leukemia treatment. (PubMed, Expert Opin Drug Saf) - "The Japanese Adverse Drug Event Report database (JADER) and WHO Adverse Drug Event Report database (VigiAccess) were used to validate the results. In FAERS and VigiAccess, the most frequent positive PT signal for gemtuzumab ozogamicin was 'febrile neutropenia.' In FAERS, the most frequent positive PT signal for inotuzumab ozogamicin was 'death.' The top five PTs with the highest signal intensity for both drugs across the three databases consistently included 'fibrin degradation products increased' and 'veno-occlusive liver disease.' Mining multiple databases enabled the identification of SOCs and AEs strongly associated with frequent adverse reactions to gemtuzumab ozogamicin and inotuzumab ozogamicin, offering valuable insights for clinical dosing guidance."

Adverse events • Journal • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hepatology • Leukemia • Neutropenia • Oncology