AML-491 Real World Practice of FLAG-Idarubicin-Venetoclax in Relapsed Refractory AML: A Single Center Experience

Abstract

Outcomes of patients with relapsed or refractory (R/R) AML remain poor. Only a small fraction achieve second remission and undergo allogeneic transplantation with long term survival. Fludarabine, cytarabine, G-CSF (FLAG)-Ida-Ven has shown promise in a phase I/II for patients with R/R AML reported by DiNardo et al. with ORR 70%; 61% achieved composite CR and 69% of those had MRD negativity. Infectious complications remain a concern, with median count recovery of 37 days in this setting. To describe the patient population, outcomes, and adverse events of those receiving FLAG-Ida-Ven for R/R AML. Retrospective study; Aug 2019-Dec 2021. Single center, major academic bone marrow transplantation center. 31 patients received FLAG-Ida-Ven with a median age of 53 years (20-78), and 68% were male. 65% of patients had adverse risk disease and 32% had TP53 mutations. 6 patients received prior allogeneic transplant. 9 patients were refractory to intensive chemotherapy, 6 to prior hypomethylating agents with venetoclax, and 13 to both. Electronic medical records were used for data extraction after IRB approval. Overall response rate, MRD status, overall survival, duration of cytopenias, transition to HSCT. 14/30 patients achieved blasts <5% in the BM (10 with morphologic leukemia-free state (MLFS), 3 with CR, 1 CRp; and 12/14 had MRD negativity. The median time to ANC recovery >500 was 35 days (20-67) and to platelet recovery >50k was 39 days (24-206). With a median follow up of 342 days, 20/31 (65%) of patients died, with a median time to death of 90 days (range 33-557). 13/30 (42%) were transplanted at a median time of 87 days (50-151). 23/31 (74%) had febrile neutropenia, 16/31 (52%) had bacteremia, 10/31 (23%) had pneumonia, and 10/31 (23%) had invasive fungal infections. Of the 13 patients who were transplanted 11/13 were alive at Day +100, with an estimated 1-year overall survival of 84% (95%CI: 0.49,0.96). FLAG-Ida-Ven is an effective regimen in the R/R setting for appropriately selected patients and may be a bridge to transplant with MRD negative remission. Infectious complications and count recovery remain a challenge and should be strongly considered as regimen related toxicity.