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<p>T-cell acute lymphoblastic leukemia (T-ALL) is a very rare hematological malignancy with a poor prognosis. Conventional cytotoxic regimens have exhibited poor tolerance in clinical practice. Preclinical researches, sparse case reports, and small-scale single-arm studies showed that venetoclax-based salvage chemotherapy had a promising clinical efficacy. However, to date, no case–control studies or prospective trials in relapsed/refractory T-ALL have been conducted to compare venetoclax-based therapies with conventional cytotoxic chemotherapies, owing to the disease’s rarity and the challenging treatment landscape. We conducted a retrospective case-cohort study comparing venetoclax-based low-intensity chemotherapy with conventional cytotoxic chemotherapies in the treatment of relapsed/refractory T-ALL. Our results indicated that venetoclax-based chemotherapy achieved comparable outcomes with heavily cytotoxic agents in complete remission rates (58.3% vs. 41.7%, <i>P</i> = 0.759), renal dysfunction (0% vs. 16.7%, <i>P</i> = 0.478), infections (50.0% vs. 75.0%, <i>P</i> = 0.400), and thrombocytopenia duration (17.0 vs. 14.5&#xa0;days, <i>P</i> = 0.434) between the venetoclax and non-venetoclax cohorts. Additionally, venetoclax-treated patients experienced fewer non-hematological adverse events, such as elevated liver enzymes than conventional cytotoxic chemotherapies (0% vs. 41.6%, <i>P</i> = 0.014), which may be attributed to reduced use of intensive cytotoxic agents like pegylated asparaginase in the venetoclax cohort. Venetoclax-based low-intensity chemotherapy might have a relatively favorable safety profile and non-inferior efficacy compared to conventional cytotoxic regimens. Therefore, venetoclax-based low-intensity chemotherapy might become a potential treatment option, especially for frail patients or those with poor hepatic function who were unable to tolerate multiple cytotoxic therapies.</p>

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Venetoclax-based low-intensity chemotherapy in the salvage treatment of relapsed/refractory T-cell acute lymphoblastic leukemia

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  • 发表日期：

    2025年4月2日

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  • Fangfei Xu,
  • Xingshuo Bao,
  • Wei Huang,
  • Kuangguo Zhou

摘要

T-cell acute lymphoblastic leukemia (T-ALL) is a very rare hematological malignancy with a poor prognosis. Conventional cytotoxic regimens have exhibited poor tolerance in clinical practice. Preclinical researches, sparse case reports, and small-scale single-arm studies showed that venetoclax-based salvage chemotherapy had a promising clinical efficacy. However, to date, no case–control studies or prospective trials in relapsed/refractory T-ALL have been conducted to compare venetoclax-based therapies with conventional cytotoxic chemotherapies, owing to the disease’s rarity and the challenging treatment landscape. We conducted a retrospective case-cohort study comparing venetoclax-based low-intensity chemotherapy with conventional cytotoxic chemotherapies in the treatment of relapsed/refractory T-ALL. Our results indicated that venetoclax-based chemotherapy achieved comparable outcomes with heavily cytotoxic agents in complete remission rates (58.3% vs. 41.7%, P = 0.759), renal dysfunction (0% vs. 16.7%, P = 0.478), infections (50.0% vs. 75.0%, P = 0.400), and thrombocytopenia duration (17.0 vs. 14.5 days, P = 0.434) between the venetoclax and non-venetoclax cohorts. Additionally, venetoclax-treated patients experienced fewer non-hematological adverse events, such as elevated liver enzymes than conventional cytotoxic chemotherapies (0% vs. 41.6%, P = 0.014), which may be attributed to reduced use of intensive cytotoxic agents like pegylated asparaginase in the venetoclax cohort. Venetoclax-based low-intensity chemotherapy might have a relatively favorable safety profile and non-inferior efficacy compared to conventional cytotoxic regimens. Therefore, venetoclax-based low-intensity chemotherapy might become a potential treatment option, especially for frail patients or those with poor hepatic function who were unable to tolerate multiple cytotoxic therapies.