Độ an toàn và hiệu quả của kháng thể đơn dòng chống chương trình chết tế bào-1 trước và sau cấy ghép tế bào gốc huyết học từ người cho cho bệnh Hodgkin đã tái phát hoặc kháng trị: một nghiên cứu hồi cứu đa trung tâm

Springer Science and Business Media LLC - Tập 112 - Trang 674-689 - 2020
Ayumu Ito1, Sung-Won Kim1, Ken-ichi Matsuoka2, Toshiro Kawakita3, Takashi Tanaka1, Yoshihiro Inamoto1, Tomomi Toubai4, Shin-ichiro Fujiwara5, Masafumi Fukaya6, Tadakazu Kondo7, Junichi Sugita8, Miho Nara9, Yuna Katsuoka10, Yosuke Imai11, Hideyuki Nakazawa12, Ichiro Kawashima13, Rika Sakai14, Arata Ishii15, Makoto Onizuka16, Tomonari Takemura17, Seitaro Terakura18, Hiroatsu Iida19, Mika Nakamae20, Kohei Higuchi21, Shinobu Tamura22, Satoshi Yoshioka23, Kazuto Togitani24, Noriaki Kawano25, Ritsuro Suzuki26, Junji Suzumiya26, Koji Izutsu27, Takanori Teshima8, Takahiro Fukuda1
1Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
2Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan
3Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan
4Division of Hematology and Cell Therapy, Department of Internal Medicine III, Yamagata University Faculty of Medicine, Yamagata, Japan
5Division of Hematology, Jichi Medical University Hospital, Shimotsuke, Japan
6Department of Stem Cell Transplantation, Shizuoka Cancer Center, Nagaizumi, Japan
7Department of Hematology, Kyoto University Hospital, Kyoto, Japan
8Department of Hematology, Hokkaido University Hospital, Sapporo, Japan;
9Department of Hematology, Akita University Hospital, Akita, Japan
10Department of Hematology, National Hospital Organization Sendai Medical Center, Sendai, Japan
11Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan
12Division of Hematology, Department of Internal Medicine, Shinshu University Hospital, Matsumoto, Japan
13Department of Hematology and Oncology, Yamanashi University Hospital, Chuo, Japan
14Department of Hematology and Medical Oncology, Kanagawa Cancer Center, Yokohama, Japan
15Department of Hematology, Blood and Marrow Transplant Center, Chiba University Hospital, Chiba, Japan
16Department of Hematology and Oncology, Tokai University Hospital, Isehara, Japan
17Division of Hematology, Department of Internal Medicine III, Hamamatsu University School of Medicine, Hamamatsu, Japan
18Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
19Department of Hematology, National Hospital Organization Nagoya Medical Center, Nagoya, Japan
20Department of Hematology, Osaka City University Hospital, Osaka, Japan
21Department of Hematology and Oncology, Osaka Women’s and Children’s Hospital, Izumi, Japan
22Department of Hematology, Wakayama Medical University Hospital, Wakayama, Japan
23Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan
24Department of Hematology, Kochi University Hospital, Kochi, Japan
25Department of Hematology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan
26Department of Oncology/Hematology, Shimane University Hospital, Izumo, Japan
27Department of Hematology, National Cancer Center Hospital, Tokyo, Japan

Tóm tắt

Chúng tôi đã tiến hành một nghiên cứu đa trung tâm về kháng thể đơn dòng chống chương trình chết tế bào-1 (anti-PD-1 mAbs) trước và sau khi cấy ghép tế bào gốc huyết học từ người cho (allo-HCT) cho bệnh nhân Hodgkin lymphoma. Anti-PD-1 mAbs đã được sử dụng cho 25 bệnh nhân trước khi thực hiện allo-HCT và cho 20 bệnh nhân sau khi cấy ghép. Trong giai đoạn trước allo-HCT, khoảng thời gian trung bình từ lần truyền cuối đến allo-HCT là 59 ngày. Sau khi thực hiện allo-HCT, 12 bệnh nhân đã phát triển hội chứng sốt không do nhiễm trùng cần sử dụng corticosteroid liều cao. Tỷ lệ tích lũy của bệnh ghép chống chủ (aGvHD) độ II–IV là 47,1%. Tám bệnh nhân đã được dự phòng GvHD bằng cyclophosphamide sau cấy ghép (PTCy) có tần suất aGvHD thấp hơn (độ II–IV, 14,6% so với 58,8%; P = 0,086). Tỷ lệ sống sót tổng quát (OS), tỷ lệ tái phát/tiến triển và tỷ lệ tử vong không do tái phát trong 1 năm là 81,3%, 27,9% và 8,4%. Trong giai đoạn sau allo-HCT, khoảng thời gian trung bình từ allo-HCT đến lần truyền đầu tiên là 589 ngày. Tỷ lệ đáp ứng tổng thể và tỷ lệ đáp ứng hoàn toàn lần lượt là 75% và 40%. Tại 100 ngày sau liệu pháp anti-PD-1, tỷ lệ tích lũy của aGvHD độ II–IV, GvHD mãn tính trung bình đến nặng, và độ độc tính liên quan đến miễn dịch độ 3–4 lần lượt là 15,0%, 30,0% và 30,0%. Trong khi tỷ lệ tái phát/tiến triển trong 1 năm là 47,4%, xác suất sống sót trong 1 năm là 89,7%. Tóm lại, các biến chứng liên quan đến miễn dịch là thường xuyên xảy ra mặc dù có những điều chỉnh về dự phòng GvHD hoặc liều lượng anti-PD-1 mAbs. Ở những bệnh nhân đã được điều trị bằng anti-PD-1-mAb, dự phòng GvHD dựa trên PTCy có thể hiệu quả.

Từ khóa

#anti-PD-1 mAbs #cấy ghép tế bào gốc huyết học #Hodgkin lymphoma #GvHD #corticosteroid #tế bào miễn dịch

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