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    Home > Active Ingredient News > Blood System > B cell NHL treatment: Can NK cell immunotherapy combined with chemotherapy and ASCT achieve "off-the-shelf"?

    B cell NHL treatment: Can NK cell immunotherapy combined with chemotherapy and ASCT achieve "off-the-shelf"?

    • Last Update: 2021-03-24
    • Source: Internet
    • Author: User
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    From February 8 to 12, 2021, the 2021 U.
    S.
    Transplantation and Cell Therapy Conference was successfully held in the form of an online virtual conference.

    The meeting announced the early results of a phase 2 trial (NCT03019640), showing that natural killer (NK) cell immunotherapy derived from cord blood combined with high-dose chemotherapy and autologous stem cell transplantation (ASCT) can induce B-cell non-Hodgkin’s lymphoma (NHL) early anti-tumor response.

    Abstract No.
    LBA15] in vitro amplification of umbilical cord blood NK cells immunotherapy and high-dose chemotherapy combined ASCT treatment of B-cell NHL: Nato Y, Kaur I, Hosing C, et al Study Overview:.
    "Off-the-shelf " Can it be possible? The researchers evaluated the potential of new cell cord blood-derived NK cell immunotherapy in B-cell NHL patients undergoing high-dose chemotherapy and ASCT therapy.

    They selected the cord blood unit for NK cell expansion on artificial antigen-presenting cells, but did not use human leukocyte antigen (HLA) for matching to provide more expansion and make "off-the-shelf" may.

    The study included 15-70-year-old B-cell NHL patients who were suitable for high-dose chemotherapy and ASCT treatment, and patients with primary central nervous system lymphoma were discharged.

    These patients need to have adequate end-organ function, the Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, and the previous collection of ≥ 2x106 CD34+ cells/Kg.

    Exclusion criteria include having received whole brain irradiation in the past month, accompanied by active hepatitis B, cirrhosis or high-grade liver fibrosis, active infection, human immunodeficiency virus (HIV) infection, or received radiotherapy.

    The patient received intravenous infusion of carmustine 12 days before transplantation (each infusion time exceeded 2 hours); 11 to 8 days before transplantation, intravenous infusion of etoposide (2 times a day, each infusion time exceeded 3h) and cytarabine (2 times a day, each infusion time is more than 1h); intravenous infusion of melphalan 7 days before transplantation (each infusion time is more than 30 minutes); 7 days to 2 days before transplantation Lenalidomide was taken orally once a day.

    In addition, CD20-positive patients received intravenous infusion of rituximab 13 to 7 days before transplantation (each infusion lasted more than 3 hours).

    Then, the patient was intravenously infused with expanded allogeneic NK cells derived from cord blood 5 days before ASCT (each infusion lasted more than 1 hour).

    Five days after ASCT, the patient began to receive filgrastim, which was administered subcutaneously once a day.

    Table 1 The primary endpoint of the study of the regimen before and after transplantation was treatment-related mortality (TRM) at 30 days, and the secondary endpoints were relapse-free survival (RFS), overall survival (OS), and NK cell persistence.

    Research results: NK cells expanded by 1552 times, amazing data.
    The researchers presented the latest data of 20 registered patients from December 2017 to July 2020.

    One patient had a rapid tumor development during the process of NK cell culture, so he was not treated in the study.

    The median age of the 19 treated patients was 60 years (range: 33-70), males accounted for 73.
    7%, diffuse large B-cell lymphoma (DLBCL) accounted for 84.
    2%, and the remaining 3 patients were mantle cell lymphoma ( MCL, n=2) or follicular lymphoma (n=1).

    More than 2/3 (68.
    4%) of patients had recurrent disease, 2 patients with MCL received first-line treatment, and 4 patients had primary refractory disease.

    The median number of treatment lines in the past was 2 (range: 1-4).

    The complete remission rate assessed by positron emission computed tomography (PET) during ASCT was 78.
    9%, the partial remission rate was 15.
    8%, and the rate of patients with disease progression was 5.
    3%.The DR site of 9 patients was 1/6 HLA, 6 patients were B site was 1/6, 3 patients A site was 1/6, B site and DR site were 2/6 There are 1 patients respectively.

    Table 2 Patient characteristics Cord blood-derived NK cells have a median increase of 1552 times (range: 317-4767) after infusion of NK products containing CD3-CD16+CD56+ phenotype.

    The median activity of NK cells derived from cord blood is 96.
    5% (range: 92%-98%).

    In peripheral blood, NK cells can be detected for an average of 2 weeks (range: 2-3).

    From week 1 to week 3, NK cells derived from cord blood showed a higher proportion of NKG2D and NKp30 activated receptors than the patient’s own NK cells.

    The study also found that the persistence of NK cells is not affected by the degree of HLA incompatibility.

    The study did not find adverse events related to cord blood NK cell immunotherapy, including infusion-related reactions, cytokine release syndrome, neurotoxicity, or graft-versus-host disease (GVHD).

    Neutrophils and platelets of all patients were rapidly implanted on the median 10th day (range: 9-13) and 13th day (range: 9-18), respectively.

    One patient died of pneumonia 2 months after ASCT, and 2 patients died of tumor progression.

    With a median follow-up of 18 months (range: 4-340), the RFS rate was 68%, and the OS rate was 84%.

    About 68.
    8% (11/16) of DLBCL patients are still in remission.

    Research conclusion: NK cell immunotherapy + chemotherapy + ASCT can be expected in the future.
    Researchers say that NK cell immunotherapy derived from expanded and high-purity cord blood combined with high-dose chemotherapy and ASCT is safe and good for the treatment of B-cell NHL patients Application prospects. References: 1.
    In B-Cell NHL, Off-the-Shelf NK Immunotherapy Shows Promise When Used With Chemotherapy and ASCT.
    cancer network.
    February 20, 2021.
    2.
    Nato Y, Kaur I, Hosing C, et al.
    Immunotherapy with ex vivo-expanded cord blood (CB)-derived nk cells combined with high-dose chemotherapy (HDC) and autologous stem cell transplant (ASCT) for B-cell non-hodgkin's lymphoma (NHL).
    Presented at: 2021 Transplant & Cellular Therapy Meetings ; February 8-12, 2021; Virtual.
    LBA15.
    Stamp "read the original text", we make progress together
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