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Daratumumab and venetoclax combined with CAGE for late R/R T-ALL/LBL patients: Single-arm, open-label, phase I study

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Abstract

The prognosis of patients diagnosed with relapsed or refractory (R/R) T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) has consistently been unsatisfactory, with limited treatment options. As reports, the CAG regimen can serve as a salvage treatment for R/R T-ALL/LBL, but there remains a subset of patients who do not benefit from it. Recent studies have indicated that daratumumab (Dara) and venetoclax (Ven) may offer promising therapeutic benefits for T-ALL/LBL. In light of these findings, we conducted a safety and efficacy evaluation of the enhanced treatment regimen, combining Dara and Ven with aclarubicin, cytarabine, granulocyte colony-stimulating factor, and etoposide (CAGE), in patients suffering from R/R T-ALL/LBL. The participants in this phase I trial were patients with R/R T-ALL/LBL who fail to standard treatment regimens. During each 28-day cycle, the patients were treated by Dara, Ven, cytarabine, aclarubicin, granulocyte colony-stimulating factor, etoposide. The primary endpoint of this study was the rate of remission. This report presents the prospective outcomes of 21 patients who received the salvage therapy of Dara and Ven combined with the CAGE regimen (Dara + Ven + CAGE). The objective remission rate (ORR) was determined to be 57.1%, while the complete remission (CR) rate was 47.6%. Notably, patients with the early T-cell precursor (ETP) subtype exhibited a significantly higher remission rate in the bone marrow compared to non-ETP patients (100% vs. 44.4%, p = 0.044). The Dara + Ven + CAGE regimen demonstrated a favorable remission rate in patients with R/R T-ALL/LBL. Moreover, the treatment was well-tolerated.

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No datasets were generated or analysed during the current study.

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Acknowledgements

We thank the histological processing and analysis services provided by immunohistochemistry, cell biology, FCM Core of Bei**g Gobroad Boren Hospital.

Funding

No funding was supported for this study.

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Authors and Affiliations

  1. Department of Lymphoma and Myeloma Research Center, Bei**g Gobroad Boren Hospital, Bei**g, 100070, China

    Hui Shi, Fan Yang, Miaomiao Cao, Teng Xu, Peihao Zheng, Yuelu Guo, Guoai Su, Shaomei Feng, Ruiting Li, Rui Liu, Haidi Liu, Lixia Ma, **aoyan Ke & Kai Hu

  2. Department of Hematology, Peking University Third Hospital, Bei**g, 100191, China

    **aoyan Ke

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  1. Hui Shi
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Contributions

K.H. and Xy. K conceived of and designed the study; H. S.performed the experiments and wrote the manuscript; F. Y., MM. C., T. X., Ph.Z., Yl. G., Ga. S., Sm. F., Rt. L., R. L., Hd.L. and Lx.M. performed the experiments; and all authors discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to **aoyan Ke or Kai Hu.

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Ethic statement

Approval of the research protocol by an Institutional Reviewer Board.

The study was approved by the Ethics Committee at the Bei**g Gobroad Boren Hospital in Bei**g Informed Consent.

Written informed consent was obtained from each patient. Clinical Trials Number: egistry and The Registration No. of the study/trial: ChiCTR2200058095.

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Shi, H., Yang, F., Cao, M. et al. Daratumumab and venetoclax combined with CAGE for late R/R T-ALL/LBL patients: Single-arm, open-label, phase I study. Ann Hematol (2024). https://doi.org/10.1007/s00277-024-05775-z

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