Venetoclax-Based Therapy Versus Intensive Chemotherapy Followed By Allogeneic-Stem Cell Transplantation for High-Risk Elderly Acute Myeloid Leukemia
Year: 2024
Type: conference-abstract
Abstract: Introduction. Acute myeloid leukemia (AML) with ELN2022 adverse risk cytogenetics have poor outcomes. The current standard of treatment for “fit” elderly patients aged 60-74 years is intensive chemotherapy (IC) with anthracycline plus cytarabine (7+3) or liposomal daunorubicin plus cytarabine (CPX-351) followed by allogeneic stem-cell transplantation (allo-SCT), when feasible. However, response rate and median overall survival (OS) remain low due to persistent disease or relapse. Non-intensive approaches based on the BCL2 inhibitor venetoclax (VEN) are commonly used for IC-ineligible AML patients based on the VIALE-A trial. However, limited data is available on the utility of VEN-based non-intensive regimens as a first-line therapy followed by allo-SCT for “fit” elderly patients with cytogenetically defined high-risk AML. Method. We retrospectively reviewed patients with newly diagnosed AML age 60-74 with chromosomal (chr.) abnormalities defining adverse risk in ELN 2022 classification, treated upfront with non-intensive VEN-based therapies compared with IC followed by allo-SCT in an international academic consortium (3 US centers [DFCI, MSKCC, Yale] and 3 Europe centers [IPC Marseille, France, CHU Nice, France, and Vilnius University Hospital, Lithuania]). Overall response rate (ORR) was defined as complete response (CR)+CR with incomplete count recovery (CRi)+Morphologic leukemia-free state (MLFS) and composite CR (cCR) as CR + CRi. OS was defined from treatment initiation to death and relapse-free survival (RFS) from the date of remission to relapse or death whichever comes first. Log-rank test was used to compare OS and RFS between groups. Cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were measured with Gray's test. Results. We included 86 patients (20 patients treated with VEN [HMA-VEN, n=16, Cladribine-Fludarabine-VEN, n=4] and 66 patients treated with IC [CPX-351, n=12, 7+3, n=44]). The median age was 66 (60-74). Pts treated with VEN-based therapies were older than IC-treated pts (69 [ranges, 61-74], vs 64 [ranges, 60-74], p=0.0001, respectively). Thirteen pts had AML with prior hematological malignancy (15.1%), and 18 pts a therapy-related AML (20.9%). Except for age, all other baseline characteristics did not differ between treatment groups. The median number of chr. abnormalities was 3 (range1-13), with most frequent cytogenetic alterations being complex karyotypes (70.0% vs. 57.6%) followed by chr. 5/7 abnormalities (45.0% vs. 50.0%), monosomal karyotype (10.0% vs. 22.7%), chr. 17 abnormalities (5% vs. 18.2%), MLL alteration (5.0% vs. 16.7%) and chr. 3 abnormalities (20.0% vs. 9.1%), in VEN vs IC groups, respectively. Mutations in TP53 were found in 15 out of the 60 tested pts (25.0%) and secondary-like mutations (Lindsley et al. Blood 2015) in 23 of the 59 tested pts (38.9%). The ORR and cCR were 90% and 90% in VEN-treated pts treated vs. 78.7% and 80.3%, in pts treated with IC, p= 0.338 and p=0.505, respectively. Allo-SCT was performed in CR in 10 (50.0%) pts vs. 48 (72.7%, p=0.101), CRi in 8 (40.0%) vs. 4 (6.0%, p=0.0001) and MLFS in 0 vs. 1 (1.5%, p=0.999), in VEN and IC groups, respectively. Two pts (10%) in the VEN group vs. 13 (19.7%) went to allo-SCT while not in remission (p=0.503). The median time from treatment initiation to allo-SCT was 159 days (interquartile ranges [IQR], 129-178) vs. 119 (IQR, 93-155, p=0.663). Median follow up was 17 mo in the VEN group (IQR, 13-24) vs. 66 (IQR, 39-77, p=<0.001). Median OS and RFS were 20 mo and 29 mo (95%CI, 0-61) vs. 19 (95%CI, 11-26) and 30 (95%CI, 22-38, p=0.508 and 0.765, respectively).The median OS for pts who underwent allo-SCT in remission was NR vs. 21 mo (95% CI, 11-79, p=0.311), in the VEN vs IC groups, respectively. Seven pts (35%) vs. 21 (31.8%) relapsed after allo-SCT, median time to relapse was 166 days (IQR, 98-210) vs. 242 (73-355) in the VEN and IC group, respectively (p=0.559). One-year NRM incidences were 22% (95%CI, 6-43) vs. 28% (95%CI, 16-42) in the VEN and IC group, respectively (p = 0.465) and 1-year CIR were 32% (95%CI, 12-54) and 21% (95%CI, 10-35) in the Ven and IC groups, respectively (p = 0.319). Conclusion. VEN-based non intensive approaches allowed successful allo-SCT with long-term disease control. This strategy may be preferred to IC for AML fit pts with adverse risk cytogenetics; however, this will have to be examined in prospective validation trials.
Source: Blood
Authors: Alexandre Iat, Jan Philipp Bewersdorf, Julia Gilhodes, Yiwen Liu, Rory M. Shallis, Leora Boussi, Andrius Zucenka, Rebecca P. Bystrom, Daniel J. DeAngelo, Guillaume Berton, Amel Soua, Kelly Ling, Luis E. Aguirre, Richard M Stone, Marlise R. Luskin, Jacqueline S. Garcia, Eric S. Winer, Evan C. Chen, Martha Wadleigh, Aaron D. Goldberg, Amer M. Zeidan, Thomas Cluzeau, Shai O. Shimony, Maximilian Stahl, Sylvain Garciaz
Institutions: Institut Paoli-Calmettes, Yale Cancer Center, Yale University, Dana-Farber Cancer Institute, Memorial Sloan Kettering Cancer Center, Vilnius University Hospital Santariskiu Klinikos, Smilow Cancer Hospital, Centre Hospitalier Universitaire de Nice, Centre National de la Recherche Scientifique, Inserm, Centre de Recherche en Cancérologie de Marseille
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4405040972