Results from the Great Britain AML Real World Evidence (ARC) Initiative - a Centre-Based Chart Review Study to Assess Treatment Outcomes of Venetoclax for the Treatment of Acute Myeloid Leukemia
Authors: O'Nions Jenny , Errico Gerardo , Floro Lajos , Murthy Vidhya , Sweeney Connor , Kaur Harpreet , Mohite Unmesh , Ayto Robert , Alvares Caroline , Goldberg Aaron D. , Moulton Kathryn , Kew Hanna , Kalinowska Ewa , Xu Yanqing , Vyas Paresh 
Published: December 2024

INTRODUCTION: Standard 1st line therapeutic strategies for patients (pts) with newly diagnosed (ND) acute myeloid leukaemia (AML) include intensive chemotherapy (IC). However, the incidence of AML increases with age and many pts are ineligible for IC due to comorbidities and/or poor performance status. In these pts efficacy and safety of venetoclax (VEN)-based combinations with azacitidine (AZA) or low dose cytarabine (LDAC) has been demonstrated in clinical trials, with subsequent approval granted by the UK Medicines and Healthcare Regulatory Agency (MHRA). it is vital to understand the outcomes and treatment patterns of patients managed in the real world (RW) setting. This study aimed to examine real world clinical effectiveness and management of VEN+AZA/LDAC in ND AML pts ineligible for IC in Great Britain (GB).

METHODS: 9 centres in England and Wales identified 167 adult pts with ND AML initiated on VEN+HMA/LDAC on or after the date of MHRA approval (28th May 2021/25th February 2022 respectively). Data collection ended 8th May 2024.

Eligible pts must have been initiated on VEN therapy at least 28 days prior to data collection, not received VEN as part of a clinical trial and not have history of other malignancies within 2 years prior to VEN. Clinical characteristics, treatment patterns and clinical outcomes were captured in a retrospective chart review. Outcomes measured included overall survival (OS), event-free survival (EFS), composite complete remission (CRc), complete remission with partial haematologic recovery (CRh) and complete remission with incomplete marrow recovery (CRi).

RESULTS: The median (range) pt age was 75.6 (53.6, 86.3), with over half reported to be ≥75 (55.7%, n=93). Females made up 42% of the total sample (n=70). 66.3% (n=108) had de novo AML and 33.7% (n=55) had clinical secondary AML. AML type was unknown for 2.4% (n=4). Of patients with ECOG performance status (PS) data available (n=125), 76% (n=95), 18.4% (n=23) and 5.6% (n=7) had an ECOG PS of &lt;1, 2 and 3 respectively.

Over half of pts had adverse ELN 2017 genetic risk classification (58.7%, n=98). Mutational status was known in 97.6% (n=163), of which 87.7% (n=143) had at least 1 genetic mutation present. Common mutations observed included IDH1/IDH2 (23.3%, n=38), TP53 (17.8%, n=29), NPM1 (11.0%, n=18), and FLT3 ITD (9.8%, n=16).

Treatment initiation was mostly performed in the inpatient setting (89.0%, n=149), with the vast majority receiving VEN+AZA (97.6%, n=163), few pts receiving VEN+LDAC (2.4%, n=4). A VEN dose ramp up was used for most pts (86.8%, n=145). BM data was available for all pts. For pts with &gt;1 BM assessment date available (n=138), the majority of first assessments post-VEN initiation were performed during cycle 1 (97.1%, n=134). 10.2%, (n=17) of patients had ≥1 in-cycle dose interruption. The median (range) number of days pts received VEN was 28 days (2,28) in cycle 1, 21 days (5,28) in cycle 2 and 14 days (5,28) in cycle 3 to cycle 6, respectively. Antifungals were prescribed in 86.6% (n=145) during cycle 1. 3.0% (n=5) proceeded to hematopoietic cell transplantation during their 1st line of therapy.

Median (range) duration of follow-up was 7.4 months (0.1,30.5) and median (range) duration of treatment was 5.3 months (0.0,31.0). VEN treatment was discontinued in 47.9% (n=80). Among those who discontinued treatment, reasons for discontinuation included adverse events (28.8%, n=23), relapse (23.8%, n=19) and insufficient response/ refractory to treatment (17.5%, n=14).

Median OS was 14.2 months (95% CI; 11.5;21.1) with 1-year OS 56.4%. Median EFS was 9.3 months (95% CI; 7.3;14.4) with 1-year EFS 44.0%. CRc was 70.7% (n=118), with CR 45.5% (n=76), CRh 6.0% (n=10) and CRi 19.1% (n=32).

Among pts achieving CRc, median (range) time to response (TTR) was 1.1 months (0.1,12.4) and median duration of response (DoR) [95% CI] was 18 months (10.4; not estimable).

CONCLUSION: Results from the GB AML ARC initiative support RW treatment effectiveness of VEN-based combinations in ND IC ineligible pts with high CRc, sustained DoR, meaningful OS and EFS outcomes. Most BM assessments were performed in cycle 1 in RW settings, highlighting the importance of early BM assessment. Outcomes reported here such as TTR, CRc, DoR and OS are similar to findings from Phase III VIALE-A trial. The results overall offer valuable insights on RW management, and associated clinical outcomes, in AML pts ineligible for IC treated with VEN-based regimens.