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Prospective randomized comparative study on rivaroxaban and LMWH for prophylaxis of post-apheresis thrombosis in adoptive T cell immunotherapy cancer patients

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Abstract

Autologous adoptive T cell immunotherapy has been recognized as an effective treatment for cancer patients. The initial qualified lymphocytes is the core element determining the immunotherapeutic outcomes clinically. Cell separator based apheresis procedure is an optimal procedure to collect adequate mono-nucleated lymphocytes to generate efficient ex vivo T cell expansions; however, potential catheter-associated femoral vein thrombosis at post-apheresis might rise an additional deteriorated morbidity for cancer patients. The emerging prophylactic medications are required at such circumstances. Therefore this study was designed to compare the prophylactic effects of rivaroxaban versus low molecular weight heparin (LMWH) in patients who had exposed during the femoral vein catheterization for apheresis. 74 Patients were randomized 1:1:1 into three groups: subcutaneous injection of LMWH, Fraxiparine (n = 23) (0.4 ml, 3800 IU/day) for 2 days, oral rivaroxaban 10 mg/d (n = 26), and oral rivaroxaban 20 mg/d (n = 25) for consecutive 2 days. The primary endpoint was to compare the venous thromboembolism (VTE) occurrence cases in one month post catheterization. There were 4 cases confirmed VTE occurrence in LMWH group with contrast to 1 case in rivaroxaban 10 mg administration group. None was seen in rivaroxaban 20 mg group (P = 0.02 as the comparison with LMWH). Meantime there was no bleeding events occurrence afterwards. Oral rivaroxaban 20 mg/day was recommendable to be considered which superior to LMWH. Although these limited data and patient volume reached the statistical difference which was able to provide the evidence proofed to compare the potency of those two anticoagulants, it could be regarded as the preliminary data provide the clinical results for cancer patients who were placed in the condition of apheresis and subsequently undergone adoptive T cell immunotherapy.

Trial registration ClinicalTrials.gov identifier, NCT03282643. Registered 16 February 2016, http://www.ClinicalTrials.gov/ NCT03282643.

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Acknowledgements

We have appreciated the cooperations and understandings from the all patients who agree to participate this study. We also thank to excellence of our nursing in the preparation of cell collections procedures.

Funding

This work was no funding supported.

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Authors and Affiliations

  1. Beijing Key Laboratory for Therapeutic Cancer Vaccines, Department of Medical Oncology, Capital Medical University Cancer Center, Beijing Shijitan Hospital, Capital Medical University, 10 Tieyi Road, Beijing, 100038, China

    Xiaoli Wang, Shuo Wang, Ni Jiang, Yanjie Zhao, Yuguang Song, Lei Zhou, Hongyan Huang, Xinna Zhou & Jun Ren

  2. Department of Surgery, Duke University Medical Center, 203 Research Drive, Suite 433, Box 2606, Durham, NC, 27710, USA

    Michael A. Morse, Amy Hobeika, Jun Ren & Herbert Kim Lyerly

Authors
  1. Xiaoli Wang
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  2. Shuo Wang
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  3. Michael A. Morse
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  4. Ni Jiang
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  5. Yanjie Zhao
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  6. Yuguang Song
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  7. Lei Zhou
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  8. Hongyan Huang
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  9. Xinna Zhou
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  11. Jun Ren
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Contributions

Dr X.W. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: J.R., H.K.L., X.W. Drafting of the manuscript: X.W., S.W., M.A.M., J.R. Critical revision of the manuscript for important intellectual content: X.W., S.W., M.A.M., J.R. Statistical analysis: X.W. and S.W. Administrative, technical, Clinical or material support:. N.J., Y.Z., Y.S., L.Z., H.H., X.Z. Study supervision: J.R., H.K.L.

Corresponding authors

Correspondence to Jun Ren or Herbert Kim Lyerly.

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Conflict of interest

The authors who have taken part in this study declare that they have nothing to conflict of interest with respect to this manuscript.

Ethical approval

This clinical trial had passed Ethics approval and consent to participate. The result of this clinical trial consent for publication. The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

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Wang, X., Wang, S., Morse, M.A. et al. Prospective randomized comparative study on rivaroxaban and LMWH for prophylaxis of post-apheresis thrombosis in adoptive T cell immunotherapy cancer patients. J Thromb Thrombolysis 47, 505–511 (2019). https://doi.org/10.1007/s11239-019-01844-7

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