- |||||||||| Review, Journal: Advancements and Challenges in the Treatment of AML. (Pubmed Central) - Apr 25, 2024
Venetoclax (VEN) with a hypomethylating agent (HMA) is the standard-of-care frontline regimen for most older patients, except perhaps for those with an IDH1 mutation where ivosidenib with azacitidine may also be considered...This article focuses on recent updates and ongoing challenges in the management of AML, with a particular focus on the ongoing challenge of secondary AML and considerations regarding the selection of initial therapy in younger patients. An overview of common side effects and toxicities associated with targeted therapies is also presented here, along with recommended strategies to mitigate these risks.
- |||||||||| Journal, Adverse events: Antibody drug conjugate adverse effects can be understood and addressed based on immune complex clearance mechanisms. (Pubmed Central) - Apr 21, 2024
We describe measurements that should help to identify those patients most likely to experience ASE due to ADC and we propose readily available treatments as well as therapies under development for other indications that should substantially reduce ASE associated with ADC. Our focus will be on the following FDA-approved ADC for which there are substantial literatures: gemtuzumab ozogamicin (Mylotarg) and inotuzumab ozogamicin; and trastuzumab emtansine (T-DM1), and trastuzumab deruxtecan (T-DXd).
- |||||||||| Mylotarg (gemtuzumab ozogamicin) / UCB, PDL, Pfizer
Enrollment closed, Trial completion date: Phase II Study of the Combination of Mitoxantrone, Etoposide and Gemtuzumab Ozogamicin (MEGO) for Patients With Acute Myeloid Leukemia Refractory to Initial Standard Induction Therapy (clinicaltrials.gov) - Apr 18, 2024 P2, N=16, Active, not recruiting, Our focus will be on the following FDA-approved ADC for which there are substantial literatures: gemtuzumab ozogamicin (Mylotarg) and inotuzumab ozogamicin; and trastuzumab emtansine (T-DM1), and trastuzumab deruxtecan (T-DXd). Completed --> Active, not recruiting | Trial completion date: Feb 2023 --> Dec 2028
- |||||||||| Daurismo (glasdegib) / Pfizer, Mylotarg (gemtuzumab ozogamicin) / UCB, PDL, Pfizer
Trial primary completion date, Combination therapy, Post-transplantation: Gemtuzumab Chemotherapy MRD Levels; Glasdegib Post-transplant, Adult Untreated, de Novo, Fav Interm Risk AML (clinicaltrials.gov) - Apr 10, 2024 P3, N=414, Recruiting, Completed --> Active, not recruiting | Trial completion date: Feb 2023 --> Dec 2028 Trial primary completion date: Apr 2023 --> Apr 2024
- |||||||||| Mylotarg (gemtuzumab ozogamicin) / UCB, PDL, Pfizer
Trial completion date, Trial primary completion date: CLAG-GO for Patients With Persistent, Relapsed or Refractory AML (clinicaltrials.gov) - Apr 4, 2024 P2, N=39, Recruiting, Trial primary completion date: Apr 2023 --> Apr 2024 Trial completion date: Feb 2025 --> Feb 2027 | Trial primary completion date: Jan 2024 --> Jun 2026
- |||||||||| Journal, Real-world evidence, Real-world: How comparable are patient outcomes in the "real-world" with populations studied in pivotal AML trials? (Pubmed Central) - Mar 31, 2024
Using data from 942 AML patients enrolled between 2012-2018, we assessed age and disease-matched control and interventional populations from published randomized trials that led to the registration of midostaurin, gemtuzumab ozogamicin, CPX-351, oral azacitidine, and venetoclax...Although real-world outcomes were comparable to some published studies, notable differences were apparent in others. If historical datasets were used to assess the impact of novel therapies, this work underscores the need to assess diverse datasets to enable geographic differences in treatment outcomes to be accounted for.
- |||||||||| Xospata (gilteritinib) / Astellas, Vyxeos (cytarabine/daunorubicin liposomal formulation) / Jazz, Nippon Shinyaku, Mylotarg (gemtuzumab ozogamicin) / UCB, PDL, Pfizer
Enrollment closed: A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations (clinicaltrials.gov) - Mar 12, 2024 P3, N=1400, Active, not recruiting, Further investigation into the incorporation of GO in the treatment algorithm for CBF-AML is needed. Recruiting --> Active, not recruiting
- |||||||||| Economy of Immunotherapy vs Chemotherapy for Relapsed/Refractory Acute Myeloid Leukemia () - Mar 8, 2024 - Abstract #ISPOR2024ISPOR_1226;
This study aimed to estimate cost-utility of targeted immunotherapies (gemtuzumab ozogamicin) and targeted non-immunotherapies (sorafenib, ivosidenib, enasidenib, gilteritinib) compared to salvage chemotherapy alone as treatment, using U.S. payer perspective. In the base-case analysis, both targeted immunotherapy and targeted non-immunotherapy were found to have a higher cost-utility when compared to salvage chemotherapy.
- |||||||||| Herceptin (trastuzumab) / Roche, Mylotarg (gemtuzumab ozogamicin) / UCB, PDL, Pfizer
A novel platform of diversified payloads to drive ADC innovation (Section 22) - Mar 5, 2024 - Abstract #AACR2024AACR_7995; The best products resulting from the screening funnel have been subjected to a multidimensional analysis taking into consideration payload properties, tumor features and antigen expression in selected populations with the aim of identifying tumor types particularly sensitive to the payload. Our multidimensional approach coupling new payload linker with innovative MoA to careful selection of patients will allow to reach unprecedented efficacy and safety profile.
- |||||||||| Besponsa (inotuzumab ozogamicin) / Pfizer, UCB, Mylotarg (gemtuzumab ozogamicin) / UCB, PDL, Pfizer
pHLIP targeted intracellular delivery of calicheamicin (Section 29) - Mar 5, 2024 - Abstract #AACR2024AACR_2575; Mylotarg, one of the first such ADCs, was voluntarily withdrawn from the market due to safety concerns...Besponsa, a related ADC, was approved for acute lymphocytic leukemia in 2017...Treatment of tumors led to the depletion of M2-TAMs within the tumor core. Thus, pHLIP-calicheamicin could be developed into an effective therapeutic for the treatment of solid tumors with abundant immuno-suppressive M2-TAMs.
- |||||||||| Mylotarg (gemtuzumab ozogamicin) / UCB, PDL, Pfizer
Journal: Outcome of Patients With Relapsed Acute Promyelocytic Leukemia. (Pubmed Central) - Mar 3, 2024 The combination of ATRA-ATO (+/- GO and idarubicin) is a highly effective salvage therapy in relapsed APL. The use of SCT may not be needed after first relapse-second remission but may be considered in subsequent relapses.
- |||||||||| Elzonris (tagraxofusp-erzs) / Menarini, Nippon Shinyaku, Mylotarg (gemtuzumab ozogamicin) / UCB, PDL, Pfizer
Enrollment open, Phase classification, Combination therapy: GO-TAG: Tagraxofusp-erzs, an IL-3 Diphtheria Fusion Protein, in Combination With Gemtuzumab Ozogamicin in Patients With Relapsed/Refractory AML (clinicaltrials.gov) - Jan 29, 2024 P1, N=36, Recruiting, Unknown status --> Completed | Trial completion date: Nov 2020 --> Sep 2023 Not yet recruiting --> Recruiting | Phase classification: P1a/1b --> P1
- |||||||||| Mylotarg (gemtuzumab ozogamicin) / UCB, PDL, Pfizer
Review, Journal: Gemtuzumab Ozogamicin in Acute Myeloid Leukemia: Efficacy, Toxicity, and Resistance Mechanisms-A Systematic Review. (Pubmed Central) - Jan 23, 2024 The drug's mechanism involves CD33 targeting and calicheamicin-induced DNA damage, leading to apoptosis and resistance mechanisms, including MDR and survival signaling, which impact treatment outcomes. Despite limited extramedullary toxicity, GO is associated with hematological side effects and hepatotoxicity.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Mylotarg (gemtuzumab ozogamicin) / UCB, PDL, Pfizer
Enrollment closed: Study of the Safety and Efficacy of Gemtuzumab Ozogamicin (GO) and Venetoclax in Patients With Relapsed or Refractory CD33+ Acute Myeloid Leukemia:Big Ten Cancer Research Consortium BTCRC-AML17-113 (clinicaltrials.gov) - Dec 12, 2023 P1, N=18, Active, not recruiting, Future research should prioritize comprehensively exploring the relationship between antibody-drug conjugates and lung diseases. Recruiting --> Active, not recruiting
- |||||||||| Mylotarg (gemtuzumab ozogamicin) / UCB, PDL, Pfizer
Journal: Fractionated vs single-dose gemtuzumab for AML. (Pubmed Central) - Nov 27, 2023 These observations may be relevant to other disulfide-linked ADCs, such as Mylotarg and Besponsa, both of which have reported similar half-lives that possibly indicate instability. No abstract available
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, Mylotarg (gemtuzumab ozogamicin) / UCB, PDL, Pfizer
Journal: Pediatric acute myeloid leukemia - novel approaches. (Pubmed Central) - Nov 20, 2023 Ongoing studies may soon define this as standard as well. After many years in which few new therapies have become available for children with AML, recent and upcoming advances may soon dramatically alter the therapeutic landscape.
- |||||||||| Vyxeos (cytarabine/daunorubicin liposomal formulation) / Jazz, Nippon Shinyaku, Mylotarg (gemtuzumab ozogamicin) / UCB, PDL, Pfizer
Trial completion date, Trial termination, Trial primary completion date: UCHMC 1812: CPX-351 and Gemtuzumab Ozogamicin in Treating Patients With Relapsed Acute Myeloid Leukemia (clinicaltrials.gov) - Nov 18, 2023 P1, N=13, Terminated, After many years in which few new therapies have become available for children with AML, recent and upcoming advances may soon dramatically alter the therapeutic landscape. Trial completion date: Jul 2025 --> Oct 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Jul 2024 --> Oct 2023; slow accrual
- |||||||||| Vyxeos (cytarabine/daunorubicin liposomal formulation) / Jazz, Nippon Shinyaku, Mylotarg (gemtuzumab ozogamicin) / UCB, PDL, Pfizer
Trial completion date, Trial primary completion date, Combination therapy: NCI-2018-01812: Liposome-encapsulated Daunorubicin-Cytarabine and Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome (clinicaltrials.gov) - Nov 18, 2023 P2, N=50, Recruiting, Trial completion date: Jul 2025 --> Oct 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Jul 2024 --> Oct 2023; slow accrual Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025
|