Sara K Silbert, Alexander W Rankin, Chloe N Hoang, Alexandra Semchenkova, Regina M Myers, Elena Zerkalenkova, Hao-Wei Wang, Alexandra E Kovach, Constance M Yuan, Dana Delgado Colon, Loïc Vasseur, Alex Bataller, Samuel John, Kaylyn Utley Lyons, Barbara Friedes, Anna Alonso-Saladrigues, Hisham Abdel-Azim, Estelle Balducci, Ahmed Assim Aljudi, Marie Balsat, D Nathan Biery, Aghiad Chamdin, Bill H Chang, Raymund S Cuevo, Barbara De Moerloose, David S Dickens, Ulrich Duffner, Nicolas Duployez, Firas El Chaer, Michelle Ann Elliott, Gabriele Escherich, Sneha Fernandes, Mandi R Fitzjohn, Zhubin Gahvari, Stephan A Grupp, Rui Rochelle He, Cynthia Harrison, Christopher B Hergott, Emily M Hsieh, Annette S Kim, Dennis J Kuo, Daniel P Larson, Benjamin J Lee, Thibaut Leguay, R Coleman Lindsley, Abhishek A Mangaonkar, Kerstin Mezger, Holly L Pacenta, Jing Pan, Marlie Provost, Latika Puri, Sunil S Raikar, Armando Martinez, Isabella Bristol, Kyle Murphy, Lauren Reiman, Michele Redell, Kelly Reed, Gabrielle Roth-Guepin, Jeremy Rubinstein, Süreyya Savaşan, Kristian Schafernak, Alexandra Stevens, Aimee Talleur, Naomi Torres Carapia, Jacques Vargaftig, Anant Vatsayan, Matthias Wölfl, Liping Zhao, Susana Rives, Vanessa A Fabrizio, Koji Sasaki, Ibrahim Aldoss, Nicolas Boissel, Susan R Rheingold, Kara L Davis, Sara Ghorashian, Elad Jacoby, Alexander Popov, Adam J Lamble, Nirali N Shah
{"title":"Project EVOLVE: an international analysis of postimmunotherapy lineage switch, an emergent form of relapse in leukemia.","authors":"Sara K Silbert, Alexander W Rankin, Chloe N Hoang, Alexandra Semchenkova, Regina M Myers, Elena Zerkalenkova, Hao-Wei Wang, Alexandra E Kovach, Constance M Yuan, Dana Delgado Colon, Loïc Vasseur, Alex Bataller, Samuel John, Kaylyn Utley Lyons, Barbara Friedes, Anna Alonso-Saladrigues, Hisham Abdel-Azim, Estelle Balducci, Ahmed Assim Aljudi, Marie Balsat, D Nathan Biery, Aghiad Chamdin, Bill H Chang, Raymund S Cuevo, Barbara De Moerloose, David S Dickens, Ulrich Duffner, Nicolas Duployez, Firas El Chaer, Michelle Ann Elliott, Gabriele Escherich, Sneha Fernandes, Mandi R Fitzjohn, Zhubin Gahvari, Stephan A Grupp, Rui Rochelle He, Cynthia Harrison, Christopher B Hergott, Emily M Hsieh, Annette S Kim, Dennis J Kuo, Daniel P Larson, Benjamin J Lee, Thibaut Leguay, R Coleman Lindsley, Abhishek A Mangaonkar, Kerstin Mezger, Holly L Pacenta, Jing Pan, Marlie Provost, Latika Puri, Sunil S Raikar, Armando Martinez, Isabella Bristol, Kyle Murphy, Lauren Reiman, Michele Redell, Kelly Reed, Gabrielle Roth-Guepin, Jeremy Rubinstein, Süreyya Savaşan, Kristian Schafernak, Alexandra Stevens, Aimee Talleur, Naomi Torres Carapia, Jacques Vargaftig, Anant Vatsayan, Matthias Wölfl, Liping Zhao, Susana Rives, Vanessa A Fabrizio, Koji Sasaki, Ibrahim Aldoss, Nicolas Boissel, Susan R Rheingold, Kara L Davis, Sara Ghorashian, Elad Jacoby, Alexander Popov, Adam J Lamble, Nirali N Shah","doi":"10.1182/blood.2024026655","DOIUrl":null,"url":null,"abstract":"<p><strong>Abstract: </strong>Lineage switch (LS), defined as the immunophenotypic transformation of acute leukemia, has emerged as a mechanism of relapse after antigen-targeted immunotherapy, which is associated with dismal outcomes. Through an international collaborative effort, we identified cases of LS after a host of antigen-targeted therapies (eg, CD19, CD22, CD38, and CD7), described how LS was diagnosed, reviewed treatment approaches, and analyzed overall outcomes for this form of postimmunotherapy relapse. Collectively, 75 cases of LS were evaluated, including 53 (70.7%) cases of B-cell acute lymphoblastic leukemia (B-ALL) transforming to acute myeloid leukemia (AML), 17 (22.7%) cases of B-ALL transforming to mixed phenotypic acute leukemia (MPAL)/acute leukemias of ambiguous lineage (ALAL), and 5 (6.7%) cases of rare LS presentation (ie, T-cell ALL to AML). An additional 10 cases with incomplete changes in immunophenotype, referred to as \"lineage drift\" were also described. With a primary focus on the 70 cases of LS from B-ALL to AML or MPAL/ALAL, LS emerged at a median of 1.5 months (range, 0-36.5) after immunotherapy, with 81.4% presenting with LS within the first 6 months from the most proximal immunotherapy. Although most involved KMT2A rearrangements (n = 45, 64.3%), other rare cytogenetic and/or molecular alterations were uniquely observed. Treatment outcomes were generally poor, with remission rates of <40%. The median overall survival after LS diagnosis was 4.8 months. Outcomes were similarly poor for those with rare immunophenotypes of LS or lineage drift. This global initiative robustly categorizes lineage changes after immunotherapy and, through enhanced understanding, establishes a foundation for improving outcomes of LS.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"437-455"},"PeriodicalIF":23.1000,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Blood","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1182/blood.2024026655","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Abstract: Lineage switch (LS), defined as the immunophenotypic transformation of acute leukemia, has emerged as a mechanism of relapse after antigen-targeted immunotherapy, which is associated with dismal outcomes. Through an international collaborative effort, we identified cases of LS after a host of antigen-targeted therapies (eg, CD19, CD22, CD38, and CD7), described how LS was diagnosed, reviewed treatment approaches, and analyzed overall outcomes for this form of postimmunotherapy relapse. Collectively, 75 cases of LS were evaluated, including 53 (70.7%) cases of B-cell acute lymphoblastic leukemia (B-ALL) transforming to acute myeloid leukemia (AML), 17 (22.7%) cases of B-ALL transforming to mixed phenotypic acute leukemia (MPAL)/acute leukemias of ambiguous lineage (ALAL), and 5 (6.7%) cases of rare LS presentation (ie, T-cell ALL to AML). An additional 10 cases with incomplete changes in immunophenotype, referred to as "lineage drift" were also described. With a primary focus on the 70 cases of LS from B-ALL to AML or MPAL/ALAL, LS emerged at a median of 1.5 months (range, 0-36.5) after immunotherapy, with 81.4% presenting with LS within the first 6 months from the most proximal immunotherapy. Although most involved KMT2A rearrangements (n = 45, 64.3%), other rare cytogenetic and/or molecular alterations were uniquely observed. Treatment outcomes were generally poor, with remission rates of <40%. The median overall survival after LS diagnosis was 4.8 months. Outcomes were similarly poor for those with rare immunophenotypes of LS or lineage drift. This global initiative robustly categorizes lineage changes after immunotherapy and, through enhanced understanding, establishes a foundation for improving outcomes of LS.
期刊介绍:
Blood, the official journal of the American Society of Hematology, published online and in print, provides an international forum for the publication of original articles describing basic laboratory, translational, and clinical investigations in hematology. Primary research articles will be published under the following scientific categories: Clinical Trials and Observations; Gene Therapy; Hematopoiesis and Stem Cells; Immunobiology and Immunotherapy scope; Myeloid Neoplasia; Lymphoid Neoplasia; Phagocytes, Granulocytes and Myelopoiesis; Platelets and Thrombopoiesis; Red Cells, Iron and Erythropoiesis; Thrombosis and Hemostasis; Transfusion Medicine; Transplantation; and Vascular Biology. Papers can be listed under more than one category as appropriate.