Project EVOLVE: an international analysis of postimmunotherapy lineage switch, an emergent form of relapse in leukemia

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.

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Publication Details

Journal
Blood
Published
2025-04-07
DOI
https://doi.org/10.1182/blood.2024026655
Citations
17
Primary Topic
Acute Lymphoblastic Leukemia research
Type
article
Field-Weighted Citation Impact
31.94

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article

Project EVOLVE: an international analysis of postimmunotherapy lineage switch, an emergent form of relapse in leukemia

Anant Vatsayan, Holly Pacenta, D. N. Biery, Dennis John Kuo et al.
17 citations
Blood
Acute Lymphoblastic Leukemia research
31.94
article

Project EVOLVE: an international analysis of postimmunotherapy lineage switch, an emergent form of relapse in leukemia

Anant Vatsayan, Holly Pacenta, D. N. Biery, Dennis John Kuo, Aghiad Chamdin, Kara L. Davis, Ahmed Abdulrahman, Marie Balsat, Alexander M. Popov, Alexandra E. Kovach, Alfredo Martı́nez, Abhishek Avinash Mangaonkar, Alexandra McLean Stevens, Sunil S. Raikar, Bill H. Chang, Alexandra Semchenkova, Constance M. Yuan, Jacques Vargaftig, Samuel John, Aimee C. Talleur, Sneha Fernandes, Cynthia Harrison, Gabriele Escherich, Alexander W. Rankin, Süreyya Savaşan, Susana Rives, Zhubin Gahvari, Annette S. Kim, Jing Pan, Susan R. Rheingold, Kelly Reed, Lauren T. Reiman, Koji Sasaki, Nirali N. Shah, Álex Bataller, David Fernando Colón, Emily M. Hsieh, Vanessa A. Fabrizio, Ulrich Duffner, Thibaut Leguay, Ibrahim Taha Aldoss, Jeremy D. Rubinstein, Kristian T. Schafernak, Adam J. Lamble, Daniel P. Larson, Sara K. Silbert, Loïc Vasseur, Firas El Chaer, Gabrielle Roth Guépin, Kerstin Mezger, Raymund S. Cuevo, Latika Puri, Barbara D. Friedes, Estelle Balducci, Michelle Ann Elliott, Anna Alonso‐Saladrigues, Hisham Abdel‐Azim, Liang Zhao, Barbara De Moerloose, David S. Dickens, Matthias Wölfl, Elena Zerkalenkova, Nicolas Boissel, Stephan A. Grupp, Sara Ghorashian, Robert Coleman Lindsley, Nicolas Duployez, Elad Jacoby, Michele S. Redell, Regina M. Myers, Christopher A. Hergott, Naomi Torres Carapia, Mandi R. Fitzjohn, Hao‐Wei Wang, Benjamin J. Lee, Kieran A. Murphy, Chloe N. Hoang, Kaylyn Utley Lyons, Rui He, Marlie R. M. Provost, Isabella Quijada Bristol
article en
17 citations

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.

BloodVol. 146(4)
Inova Health System (US), University of Southern California (US), Brigham and Women's Hospital (US), Cincinnati Children's Hospital Medical Center (US), University of Colorado Hospital (US), Hôpital Necker-Enfants Malades (FR), Loma Linda University Medical Center (US), Seattle Children's Hospital (US), National Institutes of Health (US), City Of Hope National Medical Center (US), Hospital Sant Joan de Déu Barcelona (ES), St. Jude Children's Research Hospital (US), Nationwide Children's Hospital (US), Mayo Clinic (US), Children's Hospital of Philadelphia (US), Children's National (US), Children's Hospital of Los Angeles (US), The University of Texas MD Anderson Cancer Center (US), University of Wisconsin–Madison (US), Emory University (US), Universität Hamburg (DE), Central Michigan University (US), Tel Aviv University (IL), Baylor College of Medicine (US), Chapman University (US), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), University of California, Irvine (US), Université Paris Cité (FR), Loma Linda University (US), University of Michigan (US), Sheba Medical Center (IL), Great Ormond Street Hospital (GB), Ghent University Hospital (BE), Eppendorf (Germany) (DE), Saint Louis University Hospital (US), University of Iowa Hospitals and Clinics (US), Centre Hospitalier Universitaire de Bordeaux (FR), Centre Hospitalier Universitaire de Lille (FR), University of California San Diego (US), Rady Children's Hospital-San Diego (US), Institute for Stem Cell Biology and Regenerative Medicine (IN), Cook Children's Medical Center (US), The Barbara Ann Karmanos Cancer Institute (US), Children's Hospital Colorado (US), University of California, Irvine Medical Center (US), Southwestern Medical Center (US), Assistance Publique – Hôpitaux de Paris (FR), Virginia Cancer Institute (US), Centre Hospitalier Régional et Universitaire de Nancy (FR), National Medical Research Center for Hematology (RU), University of Iowa Stead Family Children’s Hospital (US), University Medical Center Hamburg-Eppendorf (DE), Seattle Children's Hospital (US), City of Hope (US), Center for Cancer and Blood Disorders (US), Michigan United (US), Hôpital Lyon Sud (FR), Michigan Medicine (US), USC Norris Comprehensive Cancer Center (US), Dana-Farber Cancer Institute (US), Beijing Hospital (CN), HealthONE (US), Hôpital Cardiologique du Haut-Lévêque (FR), Institute for Research in Biomedicine (ES), Phoenix Children's Hospital (US), Mayo Clinic in Arizona (US), Universitätsklinikum Würzburg (DE), Sant Joan de Déu Research Foundation (ES), Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology (RU), Helen DeVos Children's Hospital (US), Children's Hospital of Michigan (US), Rocky Mountain Hospital for Children (US), UC Irvine Health (US), National Cancer Institute (US), Oregon Health and Science University Hospital (US), Hôpital Saint-Louis (FR), Mayo Clinic in Florida (US), Children's Healthcare of Atlanta (US), Texas Children's Hospital (US), Institute of Hematology & Blood Diseases Hospital (CN), Center for Cancer Research (US), Children's Cancer Center (US), Doernbecher Children's Hospital (US), Loma Linda University Children's Hospital (US), Institut de Recerca Sant Joan de Déu, Southwestern Medical Center (US), University College London (GB), University of Virginia (US), University of Colorado Anschutz Medical Campus (US), Universitat de Barcelona (ES), University of Pennsylvania (US), Institut Curie (FR), The University of Texas Southwestern Medical Center (US), University of Cincinnati Medical Center (US), University of Colorado Denver (US), Stanford University (US)
U.S. Department of Health and Human Services, Amgen, Bristol-Myers Squibb, Pfizer, Sanofi, Gilead Sciences, University of Southern California, Celgene, Children's Hospital Los Angeles, FibroGen, Jazz Pharmaceuticals, MEI Pharma, Arog Pharmaceuticals, CTI Biopharma, Incyte, Association of Community Cancer Centers, Syndax Pharmaceuticals, Y-mAbs Therapeutics, Servier, Swedish Orphan Biovitrum, MorphoSys, National Institutes of Health, Instituto de Salud Carlos III, National Cancer Institute, NIH Clinical Center, Eurostars
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Acute Lymphoblastic Leukemia research
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