Aimee Merino, Claudio C Brunstein, Ryan Shanley, Faridullah Rashid, Rose Wangen, Veronika Bachanova, Mark Juckett, Joseph Maakaron, Martin Felices, Daniel Weisdorf, Jeffrey S Miller
{"title":"N-803是一种IL-15超拮抗剂复合物,用于急性髓性白血病或骨髓增生异常综合征异体供体干细胞移植后的维持治疗;2期试验。","authors":"Aimee Merino, Claudio C Brunstein, Ryan Shanley, Faridullah Rashid, Rose Wangen, Veronika Bachanova, Mark Juckett, Joseph Maakaron, Martin Felices, Daniel Weisdorf, Jeffrey S Miller","doi":"10.1016/j.jtct.2024.09.023","DOIUrl":null,"url":null,"abstract":"<p><p>Maintenance therapy may improve natural killer (NK) cell surveillance after allogeneic donor hematopoietic cell transplant (HCT) for myeloid malignancies and represents a potential approach to improve cure rates. Interleukin-15 (IL-15) enhances lymphocyte proliferation and anti-tumor activity. In a prior Phase 1 study of an IL-15 superagonist (N-803) in patients with AML who relapsed after HCT, we observed in vivo expansion of NK cells and anti-tumor responses. The primary objective of this Phase 2 trial was to determine if post-transplant N-803 could reduce relapse. We administered N-803 (n=20) (dosed 6 mcg/kg subcutaneously (SQ) at day 60 after HCT to patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) who were in complete remission (CR). N-803 treatment was planned weekly, bi-weekly or every 4 weeks in 2 sequential cohorts. The most common adverse events after administration were self-limited injection sites skin rashes (n=20). One week after an N-803 dose, we observed enhanced NK cell proliferation and improved anti-tumor cytotoxicity without inducing immune exhaustion. Five patients who developed acute graft versus host disease (aGVHD) after N-803 responded promptly to steroids and 4 patients developed chronic GVHD. Patients receiving >4 doses of N-803 had a 3-fold decrease in relapse at two years (p=0.06). These findings support the safety, immune activation, and potential efficacy of N-803 to prevent relapse of AML/MDS after HSCT.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"N-803, an IL-15 superagonist complex as maintenance therapy after allogeneic donor stem cell transplant for acute myeloid leukemia or myelodysplastic syndrome; a Phase 2 trial.\",\"authors\":\"Aimee Merino, Claudio C Brunstein, Ryan Shanley, Faridullah Rashid, Rose Wangen, Veronika Bachanova, Mark Juckett, Joseph Maakaron, Martin Felices, Daniel Weisdorf, Jeffrey S Miller\",\"doi\":\"10.1016/j.jtct.2024.09.023\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Maintenance therapy may improve natural killer (NK) cell surveillance after allogeneic donor hematopoietic cell transplant (HCT) for myeloid malignancies and represents a potential approach to improve cure rates. Interleukin-15 (IL-15) enhances lymphocyte proliferation and anti-tumor activity. In a prior Phase 1 study of an IL-15 superagonist (N-803) in patients with AML who relapsed after HCT, we observed in vivo expansion of NK cells and anti-tumor responses. The primary objective of this Phase 2 trial was to determine if post-transplant N-803 could reduce relapse. We administered N-803 (n=20) (dosed 6 mcg/kg subcutaneously (SQ) at day 60 after HCT to patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) who were in complete remission (CR). N-803 treatment was planned weekly, bi-weekly or every 4 weeks in 2 sequential cohorts. The most common adverse events after administration were self-limited injection sites skin rashes (n=20). One week after an N-803 dose, we observed enhanced NK cell proliferation and improved anti-tumor cytotoxicity without inducing immune exhaustion. Five patients who developed acute graft versus host disease (aGVHD) after N-803 responded promptly to steroids and 4 patients developed chronic GVHD. Patients receiving >4 doses of N-803 had a 3-fold decrease in relapse at two years (p=0.06). These findings support the safety, immune activation, and potential efficacy of N-803 to prevent relapse of AML/MDS after HSCT.</p>\",\"PeriodicalId\":23283,\"journal\":{\"name\":\"Transplantation and Cellular Therapy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Transplantation and Cellular Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jtct.2024.09.023\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Transplantation and Cellular Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jtct.2024.09.023","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
N-803, an IL-15 superagonist complex as maintenance therapy after allogeneic donor stem cell transplant for acute myeloid leukemia or myelodysplastic syndrome; a Phase 2 trial.
Maintenance therapy may improve natural killer (NK) cell surveillance after allogeneic donor hematopoietic cell transplant (HCT) for myeloid malignancies and represents a potential approach to improve cure rates. Interleukin-15 (IL-15) enhances lymphocyte proliferation and anti-tumor activity. In a prior Phase 1 study of an IL-15 superagonist (N-803) in patients with AML who relapsed after HCT, we observed in vivo expansion of NK cells and anti-tumor responses. The primary objective of this Phase 2 trial was to determine if post-transplant N-803 could reduce relapse. We administered N-803 (n=20) (dosed 6 mcg/kg subcutaneously (SQ) at day 60 after HCT to patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) who were in complete remission (CR). N-803 treatment was planned weekly, bi-weekly or every 4 weeks in 2 sequential cohorts. The most common adverse events after administration were self-limited injection sites skin rashes (n=20). One week after an N-803 dose, we observed enhanced NK cell proliferation and improved anti-tumor cytotoxicity without inducing immune exhaustion. Five patients who developed acute graft versus host disease (aGVHD) after N-803 responded promptly to steroids and 4 patients developed chronic GVHD. Patients receiving >4 doses of N-803 had a 3-fold decrease in relapse at two years (p=0.06). These findings support the safety, immune activation, and potential efficacy of N-803 to prevent relapse of AML/MDS after HSCT.