Contributions
Abstract: S1563
Type: Oral Presentation
Presentation during EHA23: On Sunday, June 17, 2018 from 08:45 - 09:00
Location: Victoria Hall
Background
Venetoclax (VEN), an oral BCL-2 inhibitor, has synergistic activity when combined with hypomethylating agents.
Aims
This clinical study explores the optimal dose and efficacy of VEN in combination with decitabine (DEC) or azacitadine (AZA) in elderly AML.
Methods
This is an open-label, phase 1b, dose escalation and expansion study (NCT02203773) on the safety and efficacy of VEN, with DEC or AZA, in elderly patients (≥65 years) with untreated AML. VEN was coadministered daily with 20 mg/m2 of DEC on days 1-5 or 75 mg/m2 of AZA on days 1-7, each 28 day cycle. VEN was dosed at 400, 800, or 1200 mg in the escalation phase, and 400 or 800 mg in the expansion phase. Complete remission (CR), CR with incomplete blood count recovery (CRi), overall survival (OS) and adverse events (AEs) were evaluated.
Results
Data cutoff was July 7, 2017. Of 145 patients, 56% were male; the median age was 74 years (range: 65–86). Overall, 60, 74, and 11 patients received VEN at 400, 800, and 1200 mg, respectively. Key grade ≥3 AEs were febrile neutropenia (43%), thrombocytopenia (23%) and neutropenia (16%); pneumonia and bacteremia (all grades) occurred in 18% and 8% of patients, respectively. At 400mg of VEN, the rate of CR+CRi was 73% (76% with AZA and 71% with DEC); efficacy data are in the table. Minimal residual disease (MRD) assessment in marrow aspirates was performed at disease assessment in a central lab using multicolor flow cytometry assay; overall, 37% (36/97) of patients with CR/CRi had MRD levels below the 10-3 cutoff. Median follow up was 15.1 months.
|
| CR/CRi | Duration of CR/CRi | OS |
Patient subgroup | n | n (%) | median months | |
All VEN doses | 145 | 97 (67) | 11.3 | 17.5 |
Intermediate cytogenetic risk | 74 | 55 (74) | 12.9 | NR |
Poor cytogenetic risk | 71 | 42 (59) | 6.7 | 9.6 |
Secondary AML | 36 | 24 (67) | NR | NR |
Age ≥75 years | 62 | 40 (65) | 9.2 | 11.0 |
VEN 400 mg |
|
|
|
|
+ AZA | 29 | 22 (76) | NR | NR |
+ DEC | 31 | 22 (71) | 12.5 | 15.2 |
VEN 800 mg |
|
|
|
|
+ AZA | 37 | 21 (57) | 11.7 | 14.2 |
+ DEC | 37 | 27 (73) | 9.2 | 17.5 |
OS, overall survival; NR, not yet reached (if applicable) | ||||
Conclusion
Preliminary data suggest that 400 mg of VEN has the optimal benefit-risk profile in combination with DEC or AZA, which demonstrated a tolerable safety profile with deep responses and durable outcomes in elderly patients with AML.
Session topic: 4. Acute myeloid leukemia - Clinical
Abstract: S1563
Type: Oral Presentation
Presentation during EHA23: On Sunday, June 17, 2018 from 08:45 - 09:00
Location: Victoria Hall
Background
Venetoclax (VEN), an oral BCL-2 inhibitor, has synergistic activity when combined with hypomethylating agents.
Aims
This clinical study explores the optimal dose and efficacy of VEN in combination with decitabine (DEC) or azacitadine (AZA) in elderly AML.
Methods
This is an open-label, phase 1b, dose escalation and expansion study (NCT02203773) on the safety and efficacy of VEN, with DEC or AZA, in elderly patients (≥65 years) with untreated AML. VEN was coadministered daily with 20 mg/m2 of DEC on days 1-5 or 75 mg/m2 of AZA on days 1-7, each 28 day cycle. VEN was dosed at 400, 800, or 1200 mg in the escalation phase, and 400 or 800 mg in the expansion phase. Complete remission (CR), CR with incomplete blood count recovery (CRi), overall survival (OS) and adverse events (AEs) were evaluated.
Results
Data cutoff was July 7, 2017. Of 145 patients, 56% were male; the median age was 74 years (range: 65–86). Overall, 60, 74, and 11 patients received VEN at 400, 800, and 1200 mg, respectively. Key grade ≥3 AEs were febrile neutropenia (43%), thrombocytopenia (23%) and neutropenia (16%); pneumonia and bacteremia (all grades) occurred in 18% and 8% of patients, respectively. At 400mg of VEN, the rate of CR+CRi was 73% (76% with AZA and 71% with DEC); efficacy data are in the table. Minimal residual disease (MRD) assessment in marrow aspirates was performed at disease assessment in a central lab using multicolor flow cytometry assay; overall, 37% (36/97) of patients with CR/CRi had MRD levels below the 10-3 cutoff. Median follow up was 15.1 months.
|
| CR/CRi | Duration of CR/CRi | OS |
Patient subgroup | n | n (%) | median months | |
All VEN doses | 145 | 97 (67) | 11.3 | 17.5 |
Intermediate cytogenetic risk | 74 | 55 (74) | 12.9 | NR |
Poor cytogenetic risk | 71 | 42 (59) | 6.7 | 9.6 |
Secondary AML | 36 | 24 (67) | NR | NR |
Age ≥75 years | 62 | 40 (65) | 9.2 | 11.0 |
VEN 400 mg |
|
|
|
|
+ AZA | 29 | 22 (76) | NR | NR |
+ DEC | 31 | 22 (71) | 12.5 | 15.2 |
VEN 800 mg |
|
|
|
|
+ AZA | 37 | 21 (57) | 11.7 | 14.2 |
+ DEC | 37 | 27 (73) | 9.2 | 17.5 |
OS, overall survival; NR, not yet reached (if applicable) | ||||
Conclusion
Preliminary data suggest that 400 mg of VEN has the optimal benefit-risk profile in combination with DEC or AZA, which demonstrated a tolerable safety profile with deep responses and durable outcomes in elderly patients with AML.
Session topic: 4. Acute myeloid leukemia - Clinical