Final analysis of the phase 1b Chemotherapy and Venetoclax in Elderly Acute Myeloid Leukemia Trial (CAVEAT)
Abstract: Venetoclax plus azacitidine represents a key advance for older, unfit patients with acute myeloid leukemia (AML). The Chemotherapy and Venetoclax in Elderly AML Trial (CAVEAT) was first to combine venetoclax with intensive chemotherapy in newly diagnosed patients aged ≥65 years. In this fi...
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Elsevier
2025-04-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952925000345 |
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| author | Chong Chyn Chua Sun Loo Chun Yew Fong Stephen B. Ting Ing Soo Tiong Shaun Fleming Natasha S. Anstee Adam Ivey Michael Ashby Tse-Chieh Teh John Reynolds Andrew W. Roberts Andrew H. Wei |
| author_facet | Chong Chyn Chua Sun Loo Chun Yew Fong Stephen B. Ting Ing Soo Tiong Shaun Fleming Natasha S. Anstee Adam Ivey Michael Ashby Tse-Chieh Teh John Reynolds Andrew W. Roberts Andrew H. Wei |
| author_sort | Chong Chyn Chua |
| collection | DOAJ |
| description | Abstract: Venetoclax plus azacitidine represents a key advance for older, unfit patients with acute myeloid leukemia (AML). The Chemotherapy and Venetoclax in Elderly AML Trial (CAVEAT) was first to combine venetoclax with intensive chemotherapy in newly diagnosed patients aged ≥65 years. In this final analysis, 85 patients (median age, 71 years) were followed up for a median of 41.8 months. The CAVEAT induction combined cytarabine and idarubicin with 5 dose levels of venetoclax (50-600 mg) for up to 14 days. Two additional cohorts explored adjusted-dose venetoclax (50 mg and 100 mg) with posaconazole. CAVEAT induction was well tolerated, with low mortality (4%) and limited high-grade gastrointestinal toxicity (4%). Delayed hematologic recovery after consolidation was ameliorated by omitting idarubicin from postremission therapy. The overall response rate (ORR; complete response [CR] + CR with partial hematologic recovery + CR with incomplete count recovery) was 75%, with a median overall survival (OS) of 19.3 months (95% confidence interval [CI], 11.1-31.3). Among de novo AML, ORR was 88% and median OS was 33.1 months (95% CI, 19.3-54.3). Almost one-third have not relapsed, many benefiting from prolonged treatment-free remission (median, 17.9 months). CAVEAT induction was well tolerated and associated with high ORR that was durable, particularly for de novo AML. CAVEAT represents an effective time-limited treatment option for fit, older patients with AML. This trial was registered at https://www.anzctr.org.au as #ACTRN12616000445471. |
| format | Article |
| id | doaj-art-a38d20283aea4f61b6de08faf9f9cd7b |
| institution | DOAJ |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-a38d20283aea4f61b6de08faf9f9cd7b2025-08-20T03:08:42ZengElsevierBlood Advances2473-95292025-04-01981827183510.1182/bloodadvances.2024014900Final analysis of the phase 1b Chemotherapy and Venetoclax in Elderly Acute Myeloid Leukemia Trial (CAVEAT)Chong Chyn Chua0Sun Loo1Chun Yew Fong2Stephen B. Ting3Ing Soo Tiong4Shaun Fleming5Natasha S. Anstee6Adam Ivey7Michael Ashby8Tse-Chieh Teh9John Reynolds10Andrew W. Roberts11Andrew H. Wei12Department of Haematology, Monash Hospital and Monash University, Melbourne, Australia; Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Clinical Haematology, Northern Hospital, Melbourne, Australia; Malignant Haematology and Stem Cell Transplant Service, Alfred Hospital and Australian Centre for Blood Diseases, Monash University, Melbourne, AustraliaWalter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Clinical Haematology, Northern Hospital, Melbourne, Australia; Department of Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, AustraliaDepartment of Haematology, Austin Health, Melbourne, Australia; Olivia Newton John Cancer Research Institute, Melbourne AustraliaDepartment of Haematology, Eastern Health and Monash University, Melbourne, AustraliaDepartment of Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, AustraliaMalignant Haematology and Stem Cell Transplant Service, Alfred Hospital and Australian Centre for Blood Diseases, Monash University, Melbourne, AustraliaWalter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Biology, The University of Melbourne, Parkville, AustraliaMalignant Haematology and Stem Cell Transplant Service, Alfred Hospital and Australian Centre for Blood Diseases, Monash University, Melbourne, AustraliaMalignant Haematology and Stem Cell Transplant Service, Alfred Hospital and Australian Centre for Blood Diseases, Monash University, Melbourne, AustraliaMalignant Haematology and Stem Cell Transplant Service, Alfred Hospital and Australian Centre for Blood Diseases, Monash University, Melbourne, Australia; Department of Haematology, Eastern Health and Monash University, Melbourne, AustraliaMalignant Haematology and Stem Cell Transplant Service, Alfred Hospital and Australian Centre for Blood Diseases, Monash University, Melbourne, AustraliaWalter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia; Centre for Cancer Research, The University of Melbourne, Parkville, AustraliaWalter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Australia; Correspondence: Andrew H. Wei, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, 305 Grattan St, Melbourne, VIC 3000, Australia;Abstract: Venetoclax plus azacitidine represents a key advance for older, unfit patients with acute myeloid leukemia (AML). The Chemotherapy and Venetoclax in Elderly AML Trial (CAVEAT) was first to combine venetoclax with intensive chemotherapy in newly diagnosed patients aged ≥65 years. In this final analysis, 85 patients (median age, 71 years) were followed up for a median of 41.8 months. The CAVEAT induction combined cytarabine and idarubicin with 5 dose levels of venetoclax (50-600 mg) for up to 14 days. Two additional cohorts explored adjusted-dose venetoclax (50 mg and 100 mg) with posaconazole. CAVEAT induction was well tolerated, with low mortality (4%) and limited high-grade gastrointestinal toxicity (4%). Delayed hematologic recovery after consolidation was ameliorated by omitting idarubicin from postremission therapy. The overall response rate (ORR; complete response [CR] + CR with partial hematologic recovery + CR with incomplete count recovery) was 75%, with a median overall survival (OS) of 19.3 months (95% confidence interval [CI], 11.1-31.3). Among de novo AML, ORR was 88% and median OS was 33.1 months (95% CI, 19.3-54.3). Almost one-third have not relapsed, many benefiting from prolonged treatment-free remission (median, 17.9 months). CAVEAT induction was well tolerated and associated with high ORR that was durable, particularly for de novo AML. CAVEAT represents an effective time-limited treatment option for fit, older patients with AML. This trial was registered at https://www.anzctr.org.au as #ACTRN12616000445471.http://www.sciencedirect.com/science/article/pii/S2473952925000345 |
| spellingShingle | Chong Chyn Chua Sun Loo Chun Yew Fong Stephen B. Ting Ing Soo Tiong Shaun Fleming Natasha S. Anstee Adam Ivey Michael Ashby Tse-Chieh Teh John Reynolds Andrew W. Roberts Andrew H. Wei Final analysis of the phase 1b Chemotherapy and Venetoclax in Elderly Acute Myeloid Leukemia Trial (CAVEAT) Blood Advances |
| title | Final analysis of the phase 1b Chemotherapy and Venetoclax in Elderly Acute Myeloid Leukemia Trial (CAVEAT) |
| title_full | Final analysis of the phase 1b Chemotherapy and Venetoclax in Elderly Acute Myeloid Leukemia Trial (CAVEAT) |
| title_fullStr | Final analysis of the phase 1b Chemotherapy and Venetoclax in Elderly Acute Myeloid Leukemia Trial (CAVEAT) |
| title_full_unstemmed | Final analysis of the phase 1b Chemotherapy and Venetoclax in Elderly Acute Myeloid Leukemia Trial (CAVEAT) |
| title_short | Final analysis of the phase 1b Chemotherapy and Venetoclax in Elderly Acute Myeloid Leukemia Trial (CAVEAT) |
| title_sort | final analysis of the phase 1b chemotherapy and venetoclax in elderly acute myeloid leukemia trial caveat |
| url | http://www.sciencedirect.com/science/article/pii/S2473952925000345 |
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