Venetoclax in combination with a pediatric-inspired regimen for the treatment of newly diagnosed adults with Philadelphia chromosome-negative acute lymphoblastic leukemia

BCL-2 protein overexpression, common in B-cell acute lymphoblastic leukemia (B-ALL), including the Philadelphia chromosome (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 years (range: 18-53), 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 the 22 patients who started consolidation, 20 (91%) achieved negative minimal residual disease status (MRD-) (<0.01%) CR/CRi by flow cytometry. Of 12 patients with Ph-like B-ALL, 11 achieved MRDstatus post consolidation, with only one patient having persistent MRD at 0.01%. At diagnosis, Ph-like B-ALL cases had a trend toward a greater BCL-2-dependency compared to non-Ph-like (P=0.06). The addition of venetoclax to a pediatric-inspired regimen was safe in adults with B-ALL, leading to encouraging MRD- rate post consolidation in high-risk B-ALL, including the Ph-like subtype (clinicaltrials.gov 05157971).

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Publication Details

Journal
Haematologica
Published
2024-11-07
DOI
https://doi.org/10.3324/haematol.2024.286427
Citations
6
Primary Topic
Acute Lymphoblastic Leukemia research
Type
article
Field-Weighted Citation Impact
3.26

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article

Venetoclax in combination with a pediatric-inspired regimen for the treatment of newly diagnosed adults with Philadelphia chromosome-negative acute lymphoblastic leukemia

Caner Saygin, Wendy Stock, Diren Arda Karaoğlu, Zhaohui Gu et al.
6 citations
Haematologica
Acute Lymphoblastic Leukemia research
3.26
article

Venetoclax in combination with a pediatric-inspired regimen for the treatment of newly diagnosed adults with Philadelphia chromosome-negative acute lymphoblastic leukemia

Caner Saygin, Wendy Stock, Diren Arda Karaoğlu, Zhaohui Gu, Vaibhav Agrawal, Anthony S. Stein, Vinod A. Pullarkat, Michelle Velasquez, Amanda Blackmon, Jose Tinajero, Ahmed Aribi, Stephen J. Forman, Ibrahim Taha Aldoss, Guido Marcucci, Marjorie Robbins, Kathryn Shimamoto, Monzr M. Al Malki, Pamela S. Becker, Lucy Ghoda, Andrew Artz, Brian Ball, Karamjeet Sandhu, Amandeep Salhotra, Paul Koller, Haris Ali, Michelle Afkhami, Hoda Pourhassan, Salman Otoukesh, Jiajia Dang, Jianying Zhang, Ian Lagman
article en
6 citations

Abstract

BCL-2 protein overexpression, common in B-cell acute lymphoblastic leukemia (B-ALL), including the Philadelphia chromosome (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 years (range: 18-53), 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 the 22 patients who started consolidation, 20 (91%) achieved negative minimal residual disease status (MRD-) (<0.01%) CR/CRi by flow cytometry. Of 12 patients with Ph-like B-ALL, 11 achieved MRDstatus post consolidation, with only one patient having persistent MRD at 0.01%. At diagnosis, Ph-like B-ALL cases had a trend toward a greater BCL-2-dependency compared to non-Ph-like (P=0.06). The addition of venetoclax to a pediatric-inspired regimen was safe in adults with B-ALL, leading to encouraging MRD- rate post consolidation in high-risk B-ALL, including the Ph-like subtype (clinicaltrials.gov 05157971).

HaematologicaVol. 110(5)
City Of Hope National Medical Center (US), University of Chicago (US), City of Hope (US), Beckman Research Institute
National Institutes of Health, National Cancer Institute
Good health and well-being
Openalex Percentile: Top 8%
Acute Lymphoblastic Leukemia research
3.26
DOIOpen Access PDFOpenAlex
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