Project EVOLVE: an international analysis of postimmunotherapy lineage switch, an emergent form of relapse in leukemia
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.
Article Details
Authors (81)
Sara K. Silbert
Alexander W. Rankin
1Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Chloe N. Hoang
1Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Alexandra Semchenkova
2Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
Regina M. Myers
Elena Zerkalenkova
4Laboratory of Cytogenetics and Molecular Genetics, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
Hao-Wei Wang
Alexandra E. Kovach
6Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA
Constance M. Yuan
2Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD
Dana Delgado Colon
2National Institutes of Health, Laboratory of Pathology, NCI, Bethesda, United States
Loïc Vasseur
2Hôpital St Louis, Adolescents and young adults department, Paris, France
Alex Bataller
2Division of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
Samuel John
Kaylyn Utley Lyons
10Children's Hospital Colorado, University of Colorado School of Medicine, Denver, CO
Barbara Friedes
3Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
Anna Alonso-Saladrigues
11Leukemia and Lymphoma Department, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, Barcelona, Spain
Hisham Abdel-Azim
1Division of Transplant/Cell Therapy and Hematological Malignancies, Cancer Center, Departments of Pediatrics and Medicine, Loma Linda University School of Medicine, Children Hospital and Medical Center, Loma Linda, United States
Estelle Balducci
Université Paris Cité
Ahmed Assim Aljudi
16Department of Pathology, Children's Healthcare of Atlanta, Atlanta, GA
Marie Balsat
9Service d’Hématologie, Hospices Civils de Lyon, Hôpital Lyon Sud, Pierre-Bénite, France
D. Nathan Biery
1Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Aghiad Chamdin
18Pediatric Hematology & Oncology, Children's Hospital of Michigan/Central Michigan University, Mount Pleasant, MI
Bill H. Chang
19Division of Pediatric Hematology and Oncology, Doernbecher Children's Hospital at Oregon Health & Science University, Portland, OR
Raymund S. Cuevo
20Inova Schar Cancer Institute, Fairfax, VA
Barbara De Moerloose
David S. Dickens
19Division of Pediatric Hematology/Oncology, University of Iowa Stead Family Children’s Hospital, Iowa City, IA
Ulrich Duffner
2Section of Pediatric Bone Marrow Transplantation and Cellular Therapy, Helen DeVos Children's Hospital, Grand Rapids, United States
Nicolas Duployez
Unité Mixte de Recherche (UMR) 9020-UMR-S 1277-Canther-Cancer Heterogeneity, Plasticity and Resistance to Therapies, Institut de Recherche contre le Cancer de Lille, University of Lille, CNRS, Inserm, Centre Hospitalier Universitaire Lille, Lille, France
Firas El Chaer
Michelle Ann Elliott
26Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN
Gabriele Escherich
Sneha Fernandes
2Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
Mandi R. Fitzjohn
10Children's Hospital Colorado, University of Colorado School of Medicine, Denver, CO
Zhubin Gahvari
3University of Wisconsin-Madison - Carbone Cancer Center, Division of Hematology, Oncology, Palliative Care, Madison, United States
Stephan A. Grupp
Rui Rochelle He
30Department of Pathology, Inova Fairfax Medical Campus, Inova Health System, Falls Church, VA
Cynthia Harrison
1Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Christopher B. Hergott
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
Emily M. Hsieh
33Division of Hematology/Oncology/Transplantation and Cellular Therapy, Cancer and Blood Disease Institute, Children’s Hospital Los Angeles, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA
Annette S. Kim
1Department of Pathology, University of Michigan, Ann Arbor, MI
Dennis J. Kuo
35Division of Pediatric Hematology-Oncology, University of California San Diego/Rady Children's Hospital San Diego, San Diego, CA
Daniel P. Larson
36Division of Hematopathology, Mayo Clinic, Rochester, MN
Benjamin J. Lee
37Department of Pharmacy, Chao Family Comprehensive Cancer Center, University of California Irvine Health, Orange, CA
Thibaut Leguay
R. Coleman Lindsley
Dana-Farber Cancer Institute, Boston, Massachusetts, United States
Abhishek A. Mangaonkar
26Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN
Kerstin Mezger
40Clinic of Pediatric Hematology and Oncology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
Holly L. Pacenta
41Division of Hematology and Oncology, Cook Children's Medical Center, Fort Worth, TX
Jing Pan
Marlie Provost
43HCA HealthONE, Rocky Mountain Hospital for Children, Denver, CO
Latika Puri
44Department of Hematology, Loma Linda University Children’s Hospital, Loma Linda, CA
Sunil S. Raikar
Armando Martinez
5Flow Cytometry Unit, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD
Isabella Bristol
5Flow Cytometry Unit, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD
Kyle Murphy
5Flow Cytometry Unit, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD
Lauren Reiman
70Keck School of Medicine, University of Southern California, Los Angeles, CA
Michele Redell
3Baylor College of Medicine, Pediatrics, Houston, United States
Kelly Reed
47University of Virginia School of Nursing, Charlottesville, VA
Gabrielle Roth-Guepin
2Fi LMC, Lyon, France
Jeremy Rubinstein
33Cincinnati Children's Hospital Medical Center, Division of Oncology, Cincinnati, United States
Süreyya Savaşan
32Department of Pediatric Hematology and Oncology, Children’s Hospital of Michigan, Detroit, MI
Kristian Schafernak
52Division of Pathology and Laboratory Medicine, Phoenix Children's Hospital, Phoenix, AZ
Alexandra Stevens
1Texas Children's Hospital, Baylor College of Medicine, Department of Pediatrics, Section of Hematology and Oncology, Houston, United States
Aimee Talleur
Naomi Torres Carapia
55Children’s Hospital Los Angeles, Los Angeles, CA
Jacques Vargaftig
Anant Vatsayan
7Children's Hospital, Washington, United States
Matthias Wölfl
58Pediatric Oncology, Children's Hospital, University Hospital Würzburg, Würzburg, Germany
Liping Zhao
School of Life Science and Medicine
Susana Rives
12Institut de Recerca Sant Joan de Déu, Barcelona, Spain
Vanessa A. Fabrizio
61Pediatric Bone Marrow Transplant/Cellular Therapies, University of Colorado Anschutz/Children's Hospital Colorado, Denver, CO
Koji Sasaki
1The University of Texas MD Anderson Cancer Center, Houston, TX
Ibrahim Aldoss
Nicolas Boissel
Susan R. Rheingold
Kara L. Davis
Sara Ghorashian
Elad Jacoby
1Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
Alexander Popov
Adam J. Lamble
Nirali N. Shah