Venetoclax plus low-intensity chemotherapy for adults with acute lymphoblastic leukemia
Abstract: In acute lymphoblastic leukemia (ALL), the B-cell lymphoma 2 inhibitor venetoclax may enhance the efficacy of chemotherapy, allowing dose reductions. This phase 1b study of venetoclax plus attenuated chemotherapy enrolled 19 patients with ALL either newly diagnosed (aged ≥60 years, n = 11...
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Elsevier
2025-02-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952924006554 |
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| author | Marlise R. Luskin Shai Shimony Julia Keating Eric S. Winer Jacqueline S. Garcia Richard M. Stone Elias Jabbour Yael Flamand Kristen Stevenson Jeremy Ryan Zhihong Zeng Anthony Letai Marina Konopleva Nitin Jain Daniel J. DeAngelo |
| author_facet | Marlise R. Luskin Shai Shimony Julia Keating Eric S. Winer Jacqueline S. Garcia Richard M. Stone Elias Jabbour Yael Flamand Kristen Stevenson Jeremy Ryan Zhihong Zeng Anthony Letai Marina Konopleva Nitin Jain Daniel J. DeAngelo |
| author_sort | Marlise R. Luskin |
| collection | DOAJ |
| description | Abstract: In acute lymphoblastic leukemia (ALL), the B-cell lymphoma 2 inhibitor venetoclax may enhance the efficacy of chemotherapy, allowing dose reductions. This phase 1b study of venetoclax plus attenuated chemotherapy enrolled 19 patients with ALL either newly diagnosed (aged ≥60 years, n = 11 [B-cell, n = 8; T-cell, n = 3]) or relapsed/refractory (R/R; aged ≥18 years, n = 8 [B-cell, n = 3; T-cell, n = 5]). Venetoclax was given for 21 days with each cycle of mini–hyper-CVD (mini-HCVD; cyclophosphamide, vincristine, dexamethasone alternating with methotrexate and cytarabine). There were no dose-limiting toxicities at dose level 1 (DL1; n = 3, 400 mg/d) or DL2 (n = 6, 600 mg/d); DL2 was the recommended phase 2 dose and explored further (n = 10). The most common nonhematologic adverse events were grade ≥3 infections. There were no deaths within 60 days. There was no tumor lysis syndrome, hepatotoxicity, prolonged cytopenias, or early discontinuation for toxicity. Among patients with newly diagnosed ALL, 10 of 11 (90.9%) achieved a measurable residual disease–negative (<0.01% sensitivity) complete remission (CR) including 6 patients with hypodiploid TP53-mutated ALL. All patients in CR bridged to hematopoietic stem cell transplant (n = 9) or completed protocol (n = 1). With a median follow-up of 60 months, median disease-free survival (DFS) for patients with newly diagnosed ALL was 54.6 months (95% confidence interval [CI], 35.5 to not available), with a 2-year DFS rate of 90% (95% CI, 71-100). Among patients with R/R ALL, 3 of 8 (37.5%) achieved CR. In summary, for patients with newly diagnosed ALL, venetoclax plus mini-HCVD is well tolerated with promising efficacy. This trial was registered at www.clinicaltrials.gov as #NCT03319901. |
| format | Article |
| id | doaj-art-cbb72f4f9818444bb0bf4d49b89ff794 |
| institution | Kabale University |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-cbb72f4f9818444bb0bf4d49b89ff7942025-02-05T04:32:26ZengElsevierBlood Advances2473-95292025-02-0193617626Venetoclax plus low-intensity chemotherapy for adults with acute lymphoblastic leukemiaMarlise R. Luskin0Shai Shimony1Julia Keating2Eric S. Winer3Jacqueline S. Garcia4Richard M. Stone5Elias Jabbour6Yael Flamand7Kristen Stevenson8Jeremy Ryan9Zhihong Zeng10Anthony Letai11Marina Konopleva12Nitin Jain13Daniel J. DeAngelo14Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; Correspondence: Marlise R. Luskin, Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Dana 2056, Boston, MA 02215;Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MADepartment of Data Science, Dana-Farber Cancer Institute, Boston, MADepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MADepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MADepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MADepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TXDepartment of Data Science, Dana-Farber Cancer Institute, Boston, MADepartment of Data Science, Dana-Farber Cancer Institute, Boston, MADepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MADepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TXDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MADepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hematology and Oncology, Montefiore Einstein Comprehensive Cancer Center and Albert Einstein College of Medicine, New York, NYDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TXDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MAAbstract: In acute lymphoblastic leukemia (ALL), the B-cell lymphoma 2 inhibitor venetoclax may enhance the efficacy of chemotherapy, allowing dose reductions. This phase 1b study of venetoclax plus attenuated chemotherapy enrolled 19 patients with ALL either newly diagnosed (aged ≥60 years, n = 11 [B-cell, n = 8; T-cell, n = 3]) or relapsed/refractory (R/R; aged ≥18 years, n = 8 [B-cell, n = 3; T-cell, n = 5]). Venetoclax was given for 21 days with each cycle of mini–hyper-CVD (mini-HCVD; cyclophosphamide, vincristine, dexamethasone alternating with methotrexate and cytarabine). There were no dose-limiting toxicities at dose level 1 (DL1; n = 3, 400 mg/d) or DL2 (n = 6, 600 mg/d); DL2 was the recommended phase 2 dose and explored further (n = 10). The most common nonhematologic adverse events were grade ≥3 infections. There were no deaths within 60 days. There was no tumor lysis syndrome, hepatotoxicity, prolonged cytopenias, or early discontinuation for toxicity. Among patients with newly diagnosed ALL, 10 of 11 (90.9%) achieved a measurable residual disease–negative (<0.01% sensitivity) complete remission (CR) including 6 patients with hypodiploid TP53-mutated ALL. All patients in CR bridged to hematopoietic stem cell transplant (n = 9) or completed protocol (n = 1). With a median follow-up of 60 months, median disease-free survival (DFS) for patients with newly diagnosed ALL was 54.6 months (95% confidence interval [CI], 35.5 to not available), with a 2-year DFS rate of 90% (95% CI, 71-100). Among patients with R/R ALL, 3 of 8 (37.5%) achieved CR. In summary, for patients with newly diagnosed ALL, venetoclax plus mini-HCVD is well tolerated with promising efficacy. This trial was registered at www.clinicaltrials.gov as #NCT03319901.http://www.sciencedirect.com/science/article/pii/S2473952924006554 |
| spellingShingle | Marlise R. Luskin Shai Shimony Julia Keating Eric S. Winer Jacqueline S. Garcia Richard M. Stone Elias Jabbour Yael Flamand Kristen Stevenson Jeremy Ryan Zhihong Zeng Anthony Letai Marina Konopleva Nitin Jain Daniel J. DeAngelo Venetoclax plus low-intensity chemotherapy for adults with acute lymphoblastic leukemia Blood Advances |
| title | Venetoclax plus low-intensity chemotherapy for adults with acute lymphoblastic leukemia |
| title_full | Venetoclax plus low-intensity chemotherapy for adults with acute lymphoblastic leukemia |
| title_fullStr | Venetoclax plus low-intensity chemotherapy for adults with acute lymphoblastic leukemia |
| title_full_unstemmed | Venetoclax plus low-intensity chemotherapy for adults with acute lymphoblastic leukemia |
| title_short | Venetoclax plus low-intensity chemotherapy for adults with acute lymphoblastic leukemia |
| title_sort | venetoclax plus low intensity chemotherapy for adults with acute lymphoblastic leukemia |
| url | http://www.sciencedirect.com/science/article/pii/S2473952924006554 |
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