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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.
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