Challice L Bonifant1,2, Sarah K Tasian3,4. 1. Department of Pediatrics. 2. The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. 3. Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia. 4. Department of Pediatrics and Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Abstract
PURPOSE OF REVIEW: Exciting translational discoveries in recent years have brought realized promise of immunotherapy for children with high-risk leukemias. This review summarizes the current immunotherapeutic landscape with a focus on key clinical trials for patients with acute lymphoblastic leukemia or acute myeloid leukemia. RECENT FINDINGS: Chemotherapy resistance remains a major barrier to cure in children with high-risk leukemias. Immunotherapy approaches have potential to overcome this resistance given alternative mechanisms of action. Based upon preclinical activity and/or success in adult patients, recent clinical trials have demonstrated safety and efficacy of various mAb, antibody-drug conjugate, bispecific T-cell-engaging antibody, natural killer cell, and chimeric antigen receptor-redirected T-cell immunotherapies for children with acute lymphoblastic leukemia or acute myeloid leukemia. Food and Drug Administration approval of several of these immunotherapies has increased the pediatric leukemia therapeutic portfolio and improved clinical outcomes for previously incurable patients. SUMMARY: Several antibody-based or cellular immunotherapy modalities have demonstrated appreciable efficacy in children with relapsed or chemotherapy-refractory leukemia via early-phase clinical trials. Some studies have also identified critical biomarkers of treatment response and resistance that merit further investigation. Continued preclinical and clinical evaluation of novel immunotherapies is imperative to improve cure rates for children with high-risk leukemias.
PURPOSE OF REVIEW: Exciting translational discoveries in recent years have brought realized promise of immunotherapy for children with high-risk leukemias. This review summarizes the current immunotherapeutic landscape with a focus on key clinical trials for patients with acute lymphoblastic leukemia or acute myeloid leukemia. RECENT FINDINGS: Chemotherapy resistance remains a major barrier to cure in children with high-risk leukemias. Immunotherapy approaches have potential to overcome this resistance given alternative mechanisms of action. Based upon preclinical activity and/or success in adult patients, recent clinical trials have demonstrated safety and efficacy of various mAb, antibody-drug conjugate, bispecific T-cell-engaging antibody, natural killer cell, and chimeric antigen receptor-redirected T-cell immunotherapies for children with acute lymphoblastic leukemia or acute myeloid leukemia. Food and Drug Administration approval of several of these immunotherapies has increased the pediatric leukemia therapeutic portfolio and improved clinical outcomes for previously incurable patients. SUMMARY: Several antibody-based or cellular immunotherapy modalities have demonstrated appreciable efficacy in children with relapsed or chemotherapy-refractory leukemia via early-phase clinical trials. Some studies have also identified critical biomarkers of treatment response and resistance that merit further investigation. Continued preclinical and clinical evaluation of novel immunotherapies is imperative to improve cure rates for children with high-risk leukemias.
Authors: Elena Sotillo; David M Barrett; Kathryn L Black; Asen Bagashev; Derek Oldridge; Glendon Wu; Robyn Sussman; Claudia Lanauze; Marco Ruella; Matthew R Gazzara; Nicole M Martinez; Colleen T Harrington; Elaine Y Chung; Jessica Perazzelli; Ted J Hofmann; Shannon L Maude; Pichai Raman; Alejandro Barrera; Saar Gill; Simon F Lacey; Jan J Melenhorst; David Allman; Elad Jacoby; Terry Fry; Crystal Mackall; Yoseph Barash; Kristen W Lynch; John M Maris; Stephan A Grupp; Andrei Thomas-Tikhonenko Journal: Cancer Discov Date: 2015-10-29 Impact factor: 39.397
Authors: Alan S Gamis; Todd A Alonzo; Soheil Meshinchi; Lillian Sung; Robert B Gerbing; Susana C Raimondi; Betsy A Hirsch; Samir B Kahwash; Amy Heerema-McKenney; Laura Winter; Kathleen Glick; Stella M Davies; Patti Byron; Franklin O Smith; Richard Aplenc Journal: J Clin Oncol Date: 2014-09-20 Impact factor: 44.544
Authors: Helen E Heslop; Karen S Slobod; Martin A Pule; Gregory A Hale; Alexandra Rousseau; Colton A Smith; Catherine M Bollard; Hao Liu; Meng-Fen Wu; Richard J Rochester; Persis J Amrolia; Julia L Hurwitz; Malcolm K Brenner; Cliona M Rooney Journal: Blood Date: 2009-10-30 Impact factor: 22.113
Authors: Shannon L Maude; Theodore W Laetsch; Jochen Buechner; Susana Rives; Michael Boyer; Henrique Bittencourt; Peter Bader; Michael R Verneris; Heather E Stefanski; Gary D Myers; Muna Qayed; Barbara De Moerloose; Hidefumi Hiramatsu; Krysta Schlis; Kara L Davis; Paul L Martin; Eneida R Nemecek; Gregory A Yanik; Christina Peters; Andre Baruchel; Nicolas Boissel; Francoise Mechinaud; Adriana Balduzzi; Joerg Krueger; Carl H June; Bruce L Levine; Patricia Wood; Tetiana Taran; Mimi Leung; Karen T Mueller; Yiyun Zhang; Kapildeb Sen; David Lebwohl; Michael A Pulsipher; Stephan A Grupp Journal: N Engl J Med Date: 2018-02-01 Impact factor: 91.245
Authors: R H Rouce; H Shaim; T Sekine; G Weber; B Ballard; S Ku; C Barese; V Murali; M-F Wu; H Liu; E J Shpall; C M Bollard; K R Rabin; K Rezvani Journal: Leukemia Date: 2015-12-01 Impact factor: 11.528
Authors: Virginie Nägele; Andrea Kratzer; Gerhard Zugmaier; Chris Holland; Youssef Hijazi; Max S Topp; Nicola Gökbuget; Patrick A Baeuerle; Peter Kufer; Andreas Wolf; Matthias Klinger Journal: Exp Hematol Oncol Date: 2017-05-18
Authors: Theodore W Laetsch; Steven G DuBois; Julia Glade Bender; Margaret E Macy; Lucas Moreno Journal: Cancer Discov Date: 2020-12-04 Impact factor: 38.272
Authors: Ilias Christodoulou; Ruyan Rahnama; Jonas W Ravich; Jaesung Seo; Sergey N Zolov; Andrew N Marple; David M Markovitz; Challice L Bonifant Journal: Front Immunol Date: 2021-12-23 Impact factor: 7.561
Authors: Stuart S Winter; Amanda McCaustland; Chunxu Qu; No'eau Simeona; Nyla A Heerema; Andrew J Carroll; Brent L Wood; Gabriela Gheorghe; Charles G Mullighan; Bridget S Wilson Journal: Blood Adv Date: 2022-01-25
Authors: Bei Xie; Linjing Li; Zhewen Zhang; Lei Zhao; Juan Cheng; Cunmin Zhou; Jie Cheng; Jing Yan; Jing Chen; Juan Yi; Bei Wang; Suya Jin; Hulai Wei Journal: J Cancer Date: 2021-05-13 Impact factor: 4.207
Authors: Muna Qayed; Kwang Woo Ahn; Carrie L Kitko; Mariam H Johnson; Nirali N Shah; Christopher Dvorak; Karin Mellgren; Brian D Friend; Michael R Verneris; Wing Leung; Jacek Toporski; John Levine; Joseph Chewning; Alan Wayne; Urvi Kapoor; Brandon Triplett; Kirk R Schultz; Gregory A Yanik; Mary Eapen Journal: Blood Date: 2021-02-18 Impact factor: 25.476