Abstract
Optimal frontline use of active agents in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is prudent to improve outcomes. We report the long-term follow-up of the phase 2 trial of HyperCVAD with nelarabine and pegylated asparaginase (Original cohort). In the latest protocol iteration venetoclax was added to the induction/consolidation regimen (Venetoclax cohort). Eligible patients were adults with untreated T-ALL/LBL or after minimal therapy and with adequate organ function. Primary endpoint of this analysis was improvement in 2-year progression free survival (PFS) and overall survival (OS) with venetoclax. From Aug 2007 to Dec 2024, 145 patients, at a median age of 35.4 years, were treated; 46 (33.8%) were in the venetoclax cohort. At median follow-up (mFU) of 62.4 months, 5-year PFS, duration of response (DOR), and OS were 63.7%, 72.0% and 66.2% respectively. In the venetoclax cohort (mFU 24.4 months) 2-year PFS (87.9% versus 64.1%, p = 0.03) and 2-year DOR (93.6% versus 69.2%, p = 0.005) were superior to the original cohort (mFU 89.4 months) and 2-year OS appeared better (87.8% versus 73.9%, p = 0.16). Febrile neutropenia was the most common serious adverse event, seen in 60% patients. The addition of venetoclax to HyperCVAD-nelarabine-pegylated asparaginase was tolerable and led to improvement in DOR and PFS.
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Acknowledgements
The data was partly presented at the American Society of Hematology Annual Meeting San Diego, 2023.
Funding
The study was supported by University of Texas MD Anderson Cancer Center Grant (CA016672), University of Texas MD Anderson SPORE (C1100632) and Charif Souki Cancer Research Fund.
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FR, JS and HMK designed the manuscript. JS, HB and RS collected the data. JS, and XH did the analysis. FR, JS, NJ, NJS, TK, GB, MK, WW, AM, GI, AF, FFM, YA, PK, HMK provided patients. FR and HMK supervised the study. JS wrote the first manuscript draft. All authors reviewed and approved the final draft.
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FR has received research funding from Amgen, Astex Pharmaceuticals/Taiho Oncology, Bristol Myers Squibb/Celgene, Syos, AbbVie, Prelude, Xencor, Astellas Pharma, and Biomea Fusion; honoraria from Amgen, Bristol Myers Squibb/Celgene, Syos, AbbVie, and Astellas Pharma; has been a board of directors or advisory committee member for Astex Pharmaceuticals/Taiho Oncology; and has been a consultant for Bristol Myers Squibb/Celgene, Syos, Novartis, AbbVie, AstraZeneca, and Astellas Pharma. NJS has been a consultant for Takeda Oncology, AstraZeneca, Amgen, Novartis, and Pfizer; received research funding from Takeda Oncology, Astellas, and Stemline Therapeutics; and received honoraria from Amgen. TMK has been a consultant for AbbVie, Agios, Bristol Myers Squibb, Genentech, Jazz Pharmaceuticals, Novartis, Servier, and PinotBio; has received research funding from AbbVie, Bristol Myers Squibb, Genentech, Jazz Pharmaceuticals, Pfizer, Cellenkos, Ascentage Pharma, Galectin Therapeutics, Astellas Pharma, AstraZeneca, Amgen, Cyclacel Pharmaceuticals, Delta-Fly Pharma, Iterion Therapeutics, GlycoMimetics, and Regeneron Pharmaceuticals; and has received honoraria from Astex Pharmaceuticals. The remaining authors declare no competing financial interests. EJ has received research grants and consultancy from Amgen, Adaptive Biotechnologies, Ascentage, Autolus, Bristol-Myers Squibb, Pfizer, Takeda, Novartis, Abbvie, Genentech, ASTX, TGRX, TERN, and Johnson and Johnson. HMK has received research funding from AbbVie, Amgen, Ascentage Pharma, Bristol Myers Squibb, Daiichi Sankyo, ImmunoGen, Jazz Pharmaceuticals, and Novartis as well as honoraria from AbbVie, Amgen, Amphista Therapeutics, Ascentage Pharma, Astellas Pharma, Biologix, Curis, Ipsen, KAHR, Novartis, Pfizer, Precision BioSciences, Shenzhen TargetRx, and Takeda Oncology. All the other authors declare no relevant conflict of interest.
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Ravandi, F., Senapati, J., Jain, N. et al. Longitudinal follow up of a phase 2 trial of venetoclax added to hyper-CVAD, nelarabine and pegylated asparaginase in patients with T-cell acute lymphoblastic leukemia and lymphoma. Leukemia 38, 2717–2721 (2024). https://doi.org/10.1038/s41375-024-02414-4
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DOI: https://doi.org/10.1038/s41375-024-02414-4
