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)

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.2903-2903
• Main Authors: Senapati, Jayastu, Ravandi, Farhad, Almanza, Emmanuel, Kadia, Tapan M., Montalban-Bravo, Guillermo, Faderl, Stefan, Sasaki, Koji, Short, Nicholas J., Daver, Naval, DiNardo, Courtney D., Masarova, Lucia, Ferrajoli, Alessandra, Haddad, Fadi G., Jabbour, Elias, Borthakur, Gautam, Tan, Sheila, Pierce, Sherry, Garcia-Manero, Guillermo, Andreeff, Michael, Alvarado Valero, Yesid
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-207962

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. CPX-351 (Vyxeos) is a liposomal formulation of cytarabine and daunorubicin, at a fixed synergistic 5:1 molar ratio, and is approved by the US Food and Drug Administration (FDA) for the treatment of pediatric and adult pts with newly diagnosed therapy-related AML or AML with myelodysplasia related changes. GO is a humanized IgG4 antibody-drug conjugate against CD33 and is approved by FDA for the treatment of newly diagnosed or R/R pediatric and adult pts with CD33-expressing AML. We hypothesized that the combination of CPX351 and GO (CPX-GO) could be synergistic in a high-risk population of R/R myeloid neoplasms. Methods: We present the updated results of the single-arm pilot study (NCT03672539) of CPX351- GO combination therapy in pts with CD33 positive R/R AML or post-HMA failure HR-MDS. Pts received induction cycle (C) CPX-351 (daunorubicin 44 mg/m2 and cytarabine 100 mg/m2) administered via intravenous (IV) infusion on days (D) 1, 3, and 5. GO was administered at a dose of 3 mg/m2 (capped at 4.5 mg) IV on D1. Pts not attaining complete remission (CR) or CR with incomplete count recovery (CRi) after C1, could receive a 2nd induction cycle of CPX at the same dose, but only on D1 and D3 with GO 3 mg/m2 on D1. Pts attaining CR or CRi could receive up to 2 consolidation cycles, after a minimum of 4 weeks from the start of the previous cycle with CPX (daunorubicin 29 mg/m2 and cytarabine 65 mg/m2) IV on D1 and D3 and GO at 3 mg/m2 on D1. GO was only administered during the second consolidation cycle if there was evidence of measurable residual disease (MRD) as measured by flow cytometry. GO could also be administered as a single agent for maintenance treatment on D1 every 6 weeks, in case of persistent MRD. Response was denoted as per the ELN 2017 criteria for AML (CRc= CR+CRi; overall response [OR]=CRc + MLFS) and IWG 2018 criteria for MDS. Relapse free survival (RFS) was calculated from best overall response (OR) to relapse or death and progression free survival (PFS) from therapy initiation to relapse, change of therapy due to inadequate response/toxicity or death, whichever was earlier. Overall survival was calculated from therapy initiation to death and censored at last follow up (FU). Results: From Nov 2018-Apr 2024 47 pts have been treated. The median (med) age of the pt