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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2018

Open Access 01-12-2018 | Research highlight

CD19 CAR-T cell therapy for relapsed/refractory acute lymphoblastic leukemia: factors affecting toxicities and long-term efficacies

Authors: Li-Na Zhang, Yongping Song, Delong Liu

Published in: Journal of Hematology & Oncology | Issue 1/2018

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Abstract

The prognosis of adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) remains dismal even at this day and age. With salvage chemotherapy, only 29% (range 18 to 44%) of the patients with R/R ALL can be induced into complete remission (CR), with a median overall survival (OS) of 4 months (range 2–6 months). Blinatumomab and inotuzumab ozogamycin (IO) are immunotherapeutic agents that increased CR to 80% and extended survival to 7.7 months in this high-risk population of patients. In the last few years, chimeric antigen receptor (CAR)––engineered T cells have led to major progress in cancer immunotherapy. CD-19 CAR-T cells have been recently approved for high-risk R/R ALL and lymphoma. The data from long-term follow-up of a single-center phase I study of 19-28z CAR-T cell therapy for adult R/R ALL were just published. At the same time, a multicenter phase II study of 19-41BB CAR-T cell therapy for children and young adults with R/R B cell ALL was also published. The two studies provided fresh information with long-term follow-up. This research highlight analyzed the data and proposed future perspectives for further investigation in this rapidly evolving field.
Literature
1.
2.
Larson R, Dodge R, Burns C, Lee E, Stone R, Schulman P, Duggan D, Davey F, Sobol R, Frankel S. A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood. 1995;85(8):2025–37.PubMed
3.
Fielding AK, Richards SM, Chopra R, Lazarus HM, Litzow MR, Buck G, Durrant IJ, Luger SM, Marks DI, Franklin IM, McMillan AK, Tallman MS, Rowe JM, Goldstone AH, Medical Research Council of the United Kingdom Adult ALLWP, Eastern Cooperative Oncology G. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL): an MRC UKALL12/ECOG 2993 study. Blood. 2007;109(3):944–50.CrossRefPubMed
4.
Gökbuget N, Stanze D, Beck J, Diedrich H, Horst H-A, Hüttmann A, Kobbe G, Kreuzer K-A, Leimer L, Reichle A, Schaich M, Schwartz S, Serve H, Starck M, Stelljes M, Stuhlmann R, Viardot A, Wendelin K, Freund M, Hoelzer D. Outcome of relapsed adult lymphoblastic leukemia depends on response to salvage chemotherapy, prognostic factors, and performance of stem cell transplantation. Blood. 2012;120(10):2032–41.CrossRefPubMed
5.
Kantarjian HM, O'Brien S, Smith TL, Cortes J, Giles FJ, Beran M, Pierce S, Huh Y, Andreeff M, Koller C, Ha CS, Keating MJ, Murphy S, Freireich EJ. Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol. 2000;18(3):547–61.CrossRefPubMed
6.
Kantarjian HM, Thomas D, Ravandi F, Faderl S, Jabbour E, Garcia-Manero G, Pierce S, Shan J, Cortes J, O'Brien S. Defining the course and prognosis of adults with acute lymphocytic leukemia in first salvage after induction failure or short first remission duration. Cancer. 2010;116(24):5568–74.CrossRefPubMedPubMedCentral
7.
O'Brien S, Thomas D, Ravandi F, Faderl S, Cortes J, Borthakur G, Pierce S, Garcia-Manero G, Kantarjian HM. Outcome of adults with acute lymphocytic leukemia after second salvage therapy. Cancer. 2008;113(11):3186–91.CrossRefPubMedPubMedCentral
8.
O'Brien S, Thomas DA, Ravandi F, Faderl S, Pierce S, Kantarjian H. Results of the hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone regimen in elderly patients with acute lymphocytic leukemia. Cancer. 2008;113(8):2097–101.CrossRefPubMedPubMedCentral
9.
Oriol A, Vives S, Hernandez-Rivas JM, Tormo M, Heras I, Rivas C, Bethencourt C, Moscardo F, Bueno J, Grande C, del Potro E, Guardia R, Brunet S, Bergua J, Bernal T, Moreno MJ, Calvo C, Bastida P, Feliu E, Ribera JM, Programa Espanol de Tratamiento en Hematologia G. Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group. Haematologica. 2010;95(4):589–96.CrossRefPubMedPubMedCentral
10.
Topp MS, Gokbuget N, Stein AS, Zugmaier G, O'Brien S, Bargou RC, Dombret H, Fielding AK, Heffner L, Larson RA, Neumann S, Foa R, Litzow M, Ribera JM, Rambaldi A, Schiller G, Bruggemann M, Horst HA, Holland C, Jia C, Maniar T, Huber B, Nagorsen D, Forman SJ, Kantarjian HM. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2014;16(1):57–66.CrossRefPubMed
11.
Kantarjian H, Stein A, Gokbuget N, Fielding AK, Schuh AC, Ribera JM, Wei A, Dombret H, Foa R, Bassan R, Arslan O, Sanz MA, Bergeron J, Demirkan F, Lech-Maranda E, Rambaldi A, Thomas X, Horst HA, Bruggemann M, Klapper W, Wood BL, Fleishman A, Nagorsen D, Holland C, Zimmerman Z, Topp MS. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376(9):836–47.CrossRefPubMed
12.
Kantarjian HM, DeAngelo DJ, Stelljes M, Martinelli G, Liedtke M, Stock W, Gokbuget N, O'Brien S, Wang K, Wang T, Paccagnella ML, Sleight B, Vandendries E, Advani AS. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med. 2016;375(8):740–53.CrossRefPubMedPubMedCentral
13.
14.
15.
Sadelain M, Brentjens R, Riviere I, Park J. CD19 CAR therapy for acute lymphoblastic leukemia. Am Soc Clin Oncol Educ Book. 2015;33:e360–3.
16.
17.
Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, Mahnke YD, Melenhorst JJ, Rheingold SR, Shen A, Teachey DT, Levine BL, June CH, Porter DL, Grupp SA. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371(16):1507–17.CrossRefPubMedPubMedCentral
18.
19.
20.
21.
22.
Porter DL, Hwang WT, Frey NV, Lacey SF, Shaw PA, Loren AW, Bagg A, Marcucci KT, Shen A, Gonzalez V, Ambrose D, Grupp SA, Chew A, Zheng Z, Milone MC, Levine BL, Melenhorst JJ, June CH. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. 2015;7(303):303ra139.CrossRefPubMed
23.
24.
Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011;365(8):725–33.CrossRefPubMedPubMedCentral
25.
26.
Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, Teachey DT, Chew A, Hauck B, Wright JF, Milone MC, Levine BL, June CH. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013;368(16):1509–18.CrossRefPubMedPubMedCentral
27.
Wei G, Ding L, Wang J, Hu Y, Huang H. Advances of CD19-directed chimeric antigen receptor-modified T cells in refractory/relapsed acute lymphoblastic leukemia. Experimental Hematology & Oncology. 2017;6(1):10.CrossRef
28.
29.
30.
Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 results of ZUMA-1: a multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2017;25(1):285–95.CrossRefPubMedPubMedCentral
31.
Park JH, Rivière I, Gonen M, Wang X, Sénéchal B, Curran KJ, Sauter C, Wang Y, Santomasso B, Mead E, Roshal M, Maslak P, Davila M, Brentjens RJ, Sadelain M. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med. 2018;378:449–59.CrossRefPubMed
32.
Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M, De Moerloose B, Hiramatsu H, Schlis K, Davis KL, Martin PL, Nemecek ER, Yanik GA, Peters C, Baruchel A, Boissel N, Mechinaud F, Balduzzi A, Krueger J, June CH, Levine BL, Wood P, Taran T, Leung M, Mueller KT, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378(5):439–48.CrossRefPubMed
33.
Porter D, Frey N, Wood PA, Weng Y, Grupp SA. Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel. J Hematol Oncol. 2018;11(1):35.CrossRefPubMedPubMedCentral
34.
Kohnke T, Krupka C, Tischer J, Knosel T, Subklewe M. Increase of PD-L1 expressing B-precursor ALL cells in a patient resistant to the CD19/CD3-bispecific T cell engager antibody blinatumomab. J Hematol Oncol. 2015;8:111.CrossRefPubMedPubMedCentral
35.
Cai B, Guo M, Wang Y, Zhang Y, Yang J, Guo Y, Dai H, Yu C, Sun Q, Qiao J, Hu K, Zuo H, Dong Z, Zhang Z, Feng M, Li B, Sun Y, Liu T, Liu Z, Wang Y, Huang Y, Yao B, Han W, Ai H. Co-infusion of haplo-identical CD19-chimeric antigen receptor T cells and stem cells achieved full donor engraftment in refractory acute lymphoblastic leukemia. J Hematol Oncol. 2016;9(1):131.CrossRefPubMedPubMedCentral
36.
Hu Y, Sun J, Wu Z, Yu J, Cui Q, Pu C, Liang B, Luo Y, Shi J, Jin A, Xiao L, Huang H. Predominant cerebral cytokine release syndrome in CD19-directed chimeric antigen receptor-modified T cell therapy. J Hematol Oncol. 2016;9(1):70.CrossRefPubMedPubMedCentral
37.
Liu J, Zhong JF, Zhang X, Zhang C. Allogeneic CD19-CAR-T cell infusion after allogeneic hematopoietic stem cell transplantation in B cell malignancies. J Hematol Oncol. 2017;10(1):35.CrossRefPubMedPubMedCentral
38.
Neelapu SS, Locke FL, Bartlett NL, Lekakis L, Miklos D, Jacobson CA, Braunschweig I, Oluwole O, Siddiqi T, Lin Y, Timmerman J, Stiff PJ, Friedberg J, Flinn I, Goy A, Smith M, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Reagan P, Bot A, et al. Kte-C19 (anti-CD19 CAR T cells) induces complete remissions in patients with refractory diffuse large B-cell lymphoma (DLBCL): results from the pivotal phase 2 Zuma-1. Blood. 2016;128(22):LBA-6-LBA-6.
39.
Qin L, Lai Y, Zhao R, Wei X, Weng J, Lai P, Li B, Lin S, Wang S, Wu Q, Liang Q, Li Y, Zhang X, Wu Y, Liu P, Yao Y, Pei D, Du X, Li P. Incorporation of a hinge domain improves the expansion of chimeric antigen receptor T cells. J Hematol Oncol. 2017;10(1):68.CrossRefPubMedPubMedCentral
40.
Turtle CJ, Hanafi LA, Berger C, Gooley TA, Cherian S, Hudecek M, Sommermeyer D, Melville K, Pender B, Budiarto TM, Robinson E, Steevens NN, Chaney C, Soma L, Chen X, Yeung C, Wood B, Li D, Cao J, Heimfeld S, Jensen MC, Riddell SR, Maloney DG. CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. J Clin Invest. 2016;126(6):2123–38.CrossRefPubMedPubMedCentral
41.
Turtle CJ, Maloney DG. Clinical trials of CD19-targeted CAR-modified T cell therapy; a complex and varied landscape. Expert Rev Hematol. 2016;9(8):719–21.CrossRefPubMed
42.
Weng J, Lai P, Qin L, Lai Y, Jiang Z, Luo C, Huang X, Wu S, Shao D, Deng C, Huang L, Lu Z, Zhou M, Zeng L, Chen D, Wang Y, Chen X, Geng S, Robert W, Tang Z, He C, Li P, Du X. A novel generation 1928zT2 CAR T cells induce remission in extramedullary relapse of acute lymphoblastic leukemia. J Hematol Oncol. 2018;11(1):25.CrossRefPubMedPubMedCentral
43.
Xiao L, Huang H, Huang X, Ke X, Hu Y, Li J, Zhang Q, Hu Y, Jiang Q, Hu J, Jing H, Zhang X, Wu Z. Efficacy of anti-CD19 chimeric antigen receptor modified T(CAR-T) cell therapy in Chinese patients with relapsed/refractory acute lymphocytic leukemia in a multicenter trial. J Clin Oncol. 2017;35(15_suppl):7028.
44.
Zhu Y, Tan Y, Ou R, Zhong Q, Zheng L, Du Y, Zhang Q, Huang J. Anti-CD19 chimeric antigen receptor-modified T cells for B-cell malignancies: a systematic review of efficacy and safety in clinical trials. Eur J Haematol. 2016;96(4):389–96.CrossRefPubMed
45.
Zhu YM, Wu Z, Tan YP, Du YY LZ, Ou RM, Liu S, Pu CF, Jiang J, Wang JP, Xiao L, Zhang Q. Anti-CD19 chimeric antigen receptor T-cell therapy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia: two case reports. Medicine (Baltimore). 2016;95(51):e5676.CrossRef
46.
K-c F, Guo Y-l, Liu Y, Dai H-r, Wang Y, Lv H-y, Huang J-h, Yang Q-M, Han W-d. Cocktail treatment with EGFR-specific and CD133-specific chimeric antigen receptor-modified T cells in a patient with advanced cholangiocarcinoma. J Hematol Oncol. 2017;10(1):4.CrossRef
47.
Chong EA, Melenhorst JJ, Lacey SF, Ambrose DE, Gonzalez V, Levine BL, June CH, Schuster SJ. PD-1 blockade modulates chimeric antigen receptor (CAR)—modified T cells: refueling the CAR. Blood. 2017;129(8):1039–41.CrossRefPubMedPubMedCentral
48.
Qasim W, Zhan H, Samarasinghe S, Adams S, Amrolia P, Stafford S, Butler K, Rivat C, Wright G, Somana K, Ghorashian S, Pinner D, Ahsan G, Gilmour K, Lucchini G, Inglott S, Mifsud W, Chiesa R, Peggs KS, Chan L, Farzeneh F, Thrasher AJ, Vora A, Pule M, Veys P. Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells. Sci Transl Med. 2017;9(374) https://​doi.​org/​10.​1126/​scitranslmed.​aaj2013.
Metadata
Title
CD19 CAR-T cell therapy for relapsed/refractory acute lymphoblastic leukemia: factors affecting toxicities and long-term efficacies
Authors
Li-Na Zhang
Yongping Song
Delong Liu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2018
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-018-0593-5

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