Haematologica (Nov 2024)
Venetoclax in combination with a pediatric-inspired regimen for the treatment of newly diagnosed adults with Philadelphia chromosome-negative acute lymphoblastic leukemia
- Ibrahim Aldoss,
- Jianying Zhang,
- Kathryn Shimamoto,
- Caner Saygin,
- Marjorie Robbins,
- Vaibhav Agrawal,
- Ahmed Aribi,
- Diren Arda Karaoglu,
- Hoda Pourhassan,
- Paul Koller,
- Haris Ali,
- Amanda Blackmon,
- Salman Otoukesh,
- Karamjeet Sandhu,
- Brian Ball,
- Andrew S. Artz,
- Monzr M. Al Malki,
- Amandeep Salhotra,
- Jose Tinajero,
- Zhaohui Gu,
- Ian Lagman,
- Michelle Velasquez,
- Jacqueline Dang,
- Pamela S. Becker,
- Michelle Afkhami,
- Lucy Ghoda,
- Wendy Stock,
- Stephen J Forman,
- Anthony Stein,
- Guido Marcucci,
- Vinod Pullarkat
Affiliations
- Ibrahim Aldoss
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
- Jianying Zhang
- Department of Biostatistics, City of Hope, Duarte, CA
- Kathryn Shimamoto
- Department of Medicine-Hematology and Oncology, University of Chicago, Chicago, IL
- Caner Saygin
- Department of Medicine-Hematology and Oncology, University of Chicago, Chicago, IL
- Marjorie Robbins
- Clinical Translational Project Development, City of Hope, Duarte, CA
- Vaibhav Agrawal
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
- Ahmed Aribi
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
- Diren Arda Karaoglu
- Department of Medicine-Hematology and Oncology, University of Chicago, Chicago, IL
- Hoda Pourhassan
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
- Paul Koller
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
- Haris Ali
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
- Amanda Blackmon
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
- Salman Otoukesh
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
- Karamjeet Sandhu
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
- Brian Ball
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
- Andrew S. Artz
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
- Monzr M. Al Malki
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
- Amandeep Salhotra
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
- Jose Tinajero
- Department of Pharmacy, City of Hope, Duarte, CA
- Zhaohui Gu
- Beckman Research Institute, City of Hope, Duarte, CA, USA; Computational and Quantitative Medicine, City of Hope, Duarte, CA
- Ian Lagman
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
- Michelle Velasquez
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
- Jacqueline Dang
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
- Pamela S. Becker
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA; Hematological Malignancies Translational Science, City of Hope, Duarte, CA
- Michelle Afkhami
- Department of Pathology, City of Hope, Duarte, CA
- Lucy Ghoda
- Beckman Research Institute, City of Hope, Duarte, CA, USA; Hematological Malignancies Translational Science, City of Hope, Duarte, CA, USA; Department of Research Business Operations, City of Hope, Duarte, CA
- Wendy Stock
- Department of Medicine-Hematology and Oncology, University of Chicago, Chicago, IL
- Stephen J Forman
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
- Anthony Stein
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
- Guido Marcucci
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA; Beckman Research Institute, City of Hope, Duarte, CA, USA; Hematological Malignancies Translational Science, City of Hope, Duarte, CA
- Vinod Pullarkat
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
- DOI
- https://doi.org/10.3324/haematol.2024.286427
- Journal volume & issue
-
Vol. 999,
no. 1
Abstract
BCL-2 protein overexpression, common in B-cell acute lymphoblastic leukemia (B-ALL), including the Philadelphia (Ph)-like subtype, mediates leukemic cell survival. We treated 24 patients with 14 days of BCL-2 inhibitor, venetoclax, 400 mg daily (dose level 1) during induction and consolidation cycles combined with the CALGB 10403 regimen in newly diagnosed adults with Ph-negative B-ALL. Median age was 31 (range: 18-53) years, 92% were Hispanic, and 12 (50%) patients had Ph-like ALL. No dose limiting toxicity occurred in the phase 1 part. Median times to neutrophil and platelet count recovery were 20 and 21 days from start of induction, respectively. The most common grade ≥3 treatment-related adverse events were leukopenia (96%), neutropenia (83%), anemia (83%), thrombocytopenia (79%), lymphopenia (71%), hyperbilirubinemia (38%), and elevated ALT (33%). One patient with non-Ph-like ALL died from asparaginase-associated pancreatitis, and 23 (96%) patients achieved complete remission (CR) or CR with incomplete count recovery (CRi) following induction with or without extended induction phase. Of 22 patients who started consolidation, 20 (91%) achieved negative minimal residual disease status (MRD-) (
