The aml Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the aml Hub cannot guarantee the accuracy of translated content. The aml and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.
The AML Hub is an independent medical education platform, sponsored by Astellas, Daiichi Sankyo, Johnson & Johnson, Kura Oncology and Syndax, and has been supported through educational grants from Bristol Myers Squibb and the Hippocrate Conference Institute, an association of the Servier Group. The funders are allowed no direct influence on our content. The levels of sponsorship listed are reflective of the amount of funding given. View funders.
Now you can support HCPs in making informed decisions for their patients
Your contribution helps us continuously deliver expertly curated content to HCPs worldwide. You will also have the opportunity to make a content suggestion for consideration and receive updates on the impact contributions are making to our content.
Find out moreCreate an account and access these new features:
Bookmark content to read later
Select your specific areas of interest
View aml content recommended for you
Older patients with acute myeloid leukemia (AML) are often unable to tolerate intensive chemotherapy (IC), and so have limited treatment options.1 Less intensive options, such as low-dose cytarabine (LDAC) have been associated with poor response rates.2 There is currently an unmet need for more effective and less toxic treatment options for older patients with AML.
Associate Professor Andrew Wei, from The Alfred Hospital, Melbourne, AU, and colleagues conducted an open-label, multicenter, multinational, dose-escalation/dose-expansion phase Ib/II trial (NCT02287233) investigating the safety and preliminary efficacy of venetoclax,3 a selective B cell leukemia inhibitor, together with LDAC in older patients with AML, ineligible for intensive chemotherapy. Patients were accepted into the study providing they had no prior treatments for their AML, except for hypomethylating agents (HMA). The primary objectives of the study were safety, pharmacokinetics (PK), maximum tolerated dose and recommended phase II dose of venetoclax.
The key endpoints of the study were safety, tolerability, safety, response rates, duration of response (DOR) and overall survival (OS). Objectives of dose expansion were to obtain preliminary estimates of efficacy, including: overall response rate (ORR), complete remission (CR), and complete remission with incomplete blood count recovery (CRi).
Table 1: Adverse Events (AEs) affecting >20% of patients, with 55% of patients needing venetoclax dose interruptions due to AEs
AEs |
Patients (%) |
---|---|
Febrile neutropenia |
34 (42) |
Thrombocytopenia |
31 (38) |
Decreased WBC count |
28 (34) |
Anemia |
22 (27) |
Neutropenia |
22 (27) |
Platelet count decreased |
20 (24) |
Table 2: Serious AEs affecting >5% of patients
Serious AEs |
Patients (%) |
---|---|
Anemia |
25 (31) |
Febrile neutropenia |
22 (27) |
Pneumonia |
8 (10) |
AML progression |
7 (9) |
Sepsis |
6 (7) |
Table 3: CR and CRi rates by patient subgroups
|
Rate of response (%) |
||
---|---|---|---|
CR |
CRi |
||
All |
26 |
28 |
|
Cytogenic risk |
Intermediate |
35 |
29 |
|
Poor |
15 |
27 |
Prior HMA |
Yes |
4 |
29 |
|
No |
34 |
28 |
AML |
De Novo |
45 |
26 |
|
Secondary |
5 |
30 |
The combination of venetoclax and LDAC is tolerable and associated with high rates of remission in elderly patients with previously untreated AML. The rapid induction and durable length of remission make this combination an attractive treatment option for patients ineligible for intensive chemotherapy.
References