Venetoclax in combination with a pediatric-inspired regimen for the treatment of newly diagnosed adults with Philadelphia chromosome-negative acute lymphoblastic leukemia
Year: 2024
Type: article
Study design: Clinical Trial
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).
Source: Haematologica
Authors: 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
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,157
Awards: G772794905, G9000092632
OpenAlex ID: W4404149607