1,111
Views
27
CrossRef citations to date
0
Altmetric
Review

New targeted therapies for relapsed pediatric acute lymphoblastic leukemia

, , &
Pages 725-736 | Received 08 May 2017, Accepted 22 Jun 2017, Published online: 05 Jul 2017

References

  • Siegel DA, King J, Tai E, et al. Cancer incidence rates and trends among children and adolescents in the United States, 2001–2009. Pediatrics. 2014;134(4):e945–955.
  • Hunger SP, Lu X, Devidas M, et al. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children’s oncology group. J Clin Oncol. 2012;30(14):1663–1669.
  • Raetz EA, Bhatla T. Where do we stand in the treatment of relapsed acute lymphoblastic leukemia? Hematology Am Soc Hematol Educ Program. 2012;2012:129–136.
  • Schultz KR, Pullen DJ, Sather HN, et al. Risk- and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children’s Cancer Group (CCG). Blood. 2007;109(3):926–935.
  • Carroll WL, Raetz EA. Clinical and laboratory biology of childhood acute lymphoblastic leukemia. J Pediatr. 2012;160(1):10–18.
  • Locatelli F, Schrappe M, Bernardo ME, et al. How I treat relapsed childhood acute lymphoblastic leukemia. Blood. 2012;120(14):2807–2816.
  • Raetz EA, Borowitz MJ, Devidas M, et al. Reinduction platform for children with first marrow relapse of acute lymphoblastic leukemia: a Children’s Oncology Group study[corrected]. J Clin Oncol. 2008;26(24):3971–3978.
  • Nguyen K, Devidas M, Cheng SC, et al. Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children’s Oncology Group study. Leukemia. 2008;22(12):2142–2150.
  • Eapen M, Zhang MJ, Devidas M, et al. Outcomes after HLA-matched sibling transplantation or chemotherapy in children with acute lymphoblastic leukemia in a second remission after an isolated central nervous system relapse: a collaborative study of the Children’s Oncology Group and the Center for International Blood And Marrow Transplant Research. Leukemia. 2008;22(2):281–286.
  • Freyer DR, Devidas M, La M, et al. Postrelapse survival in childhood acute lymphoblastic leukemia is independent of initial treatment intensity: a report from the Children’s Oncology Group. Blood. 2011;117(11):3010–3015.
  • Pulsipher MA, Langholz B, Wall DA, et al. Risk factors and timing of relapse after allogeneic transplantation in pediatric ALL: for whom and when should interventions be tested? Bone Marrow Transplant. 2015;50(9):1173–1179.
  • Bhatla T, Jones CL, Meyer JA, et al. The biology of relapsed acute lymphoblastic leukemia: opportunities for therapeutic interventions. J Pediatr Hematol Oncol. 2014;36(6):413–418.
  • Bader P, Kreyenberg H, Henze GH, et al. Prognostic value of minimal residual disease quantification before allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia: the ALL-REZ BFM Study Group. J Clin Oncol. 2009;27(3):377–384.
  • Gaynon PS, Harris RE, Altman AJ, et al. Bone marrow transplantation versus prolonged intensive chemotherapy for children with acute lymphoblastic leukemia and an initial bone marrow relapse within 12 months of the completion of primary therapy: Children’s Oncology Group study CCG-1941. J Clin Oncol. 2006;24(19):3150–3156.
  • Eckert C, Henze G, Seeger K, et al. Use of allogeneic hematopoietic stem-cell transplantation based on minimal residual disease response improves outcomes for children with relapsed acute lymphoblastic leukemia in the intermediate-risk group. J Clin Oncol. 2013;31(21):2736–2742.
  • Bader P, Kreyenberg H, von Stackelberg A. et al. Monitoring of minimal residual disease after allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia allows for the identification of impending relapse: results of the ALL-BFM-SCT 2003 trial. J Clin Oncol. 2015;33(11):1275–1284.
  • Tallen G, Ratei R, Mann G, et al. Long-term outcome in children with relapsed acute lymphoblastic leukemia after time-point and site-of-relapse stratification and intensified short-course multidrug chemotherapy: results of trial ALL-REZ BFM 90. J Clin Oncol. 2010;28(14):2339–2347.
  • Klumper E, Pieters R, Veerman AJ, et al. In vitro cellular drug resistance in children with relapsed/refractory acute lymphoblastic leukemia. Blood. 1995;86(10):3861–3868.
  • Borowitz MJ, Devidas M, Hunger SP, et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children’s Oncology Group study. Blood. 2008;111(12):5477–5485.
  • Hongo T, Fujii Y. In vitro chemosensitivity of lymphoblasts at relapse in childhood leukemia using the MTT assay. Int J Hematol. 1991;54(3):219–230.
  • Hogan LE, Meyer JA, Yang J, et al. Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies. Blood. 2011;118(19):5218–5226.
  • Yang JJ, Bhojwani D, Yang W, et al. Genome-wide copy number profiling reveals molecular evolution from diagnosis to relapse in childhood acute lymphoblastic leukemia. Blood. 2008;112(10):4178–4183.
  • Bhojwani D, Kang H, Moskowitz NP, et al. Biologic pathways associated with relapse in childhood acute lymphoblastic leukemia: a Children’s Oncology Group study. Blood. 2006;108(2):711–717.
  • Mullighan CG, Phillips LA, Su X, et al. Genomic analysis of the clonal origins of relapsed acute lymphoblastic leukemia. Science. 2008;322(5906):1377–1380.
  • Mullighan CG, Goorha S, Radtke I, et al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature. 2007;446(7137):758–764.
  • Mullighan CG, Su X, Zhang J, et al. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med. 2009;360(5):470–480.
  • Jones CL, Bhatla T, Blum R, et al. Loss of TBL1XR1 disrupts glucocorticoid receptor recruitment to chromatin and results in glucocorticoid resistance in a B-lymphoblastic leukemia model. J Biol Chem. 2014;289(30):20502–20515.
  • van Galen JC, Kuiper RP, van Emst L. et al. BTG1 regulates glucocorticoid receptor autoinduction in acute lymphoblastic leukemia. Blood. 2010;115(23):4810–4819.
  • Irving JA, Minto L, Bailey S, et al. Loss of heterozygosity and somatic mutations of the glucocorticoid receptor gene are rarely found at relapse in pediatric acute lymphoblastic leukemia but may occur in a subpopulation early in the disease course. Cancer Res. 2005;65(21):9712–9718.
  • Dandekar S, Romanos-Sirakis E, Pais F, et al. Wnt inhibition leads to improved chemosensitivity in paediatric acute lymphoblastic leukaemia. Br J Haematol. 2014;167(1):87–99.
  • Jones CL, Gearheart CM, Fosmire S, et al. MAPK signaling cascades mediate distinct glucocorticoid resistance mechanisms in pediatric leukemia. Blood. 2015;126(19):2202–2212.
  • Irving J, Matheson E, Minto L, et al. Ras pathway mutations are prevalent in relapsed childhood acute lymphoblastic leukemia and confer sensitivity to MEK inhibition. Blood. 2014;124(23):3420–3430.
  • Ma X, Edmonson M, Yergeau D, et al. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia. Nat Commun. 2015;6:6604.
  • Meyer JA, Wang J, Hogan LE, et al. Relapse-specific mutations in NT5C2 in childhood acute lymphoblastic leukemia. Nat Genet. 2013;45(3):290–294.
  • Tzoneva G, Perez-Garcia A, Carpenter Z, et al. Activating mutations in the NT5C2 nucleotidase gene drive chemotherapy resistance in relapsed ALL. Nat Med. 2013;19(3):368–371.
  • Li B, Li H, Bai Y, et al. Negative feedback-defective PRPS1 mutants drive thiopurine resistance in relapsed childhood ALL. Nat Med. 2015;21(6):563–571.
  • Diouf B, Cheng Q, Krynetskaia NF, et al. Somatic deletions of genes regulating MSH2 protein stability cause DNA mismatch repair deficiency and drug resistance in human leukemia cells. Nat Med. 2011;17(10):1298–1303.
  • Madhusoodhan PP, Evensen NA, Saliba J et al. Measurement of phosphorylated ERK as a prognostic and predictive marker for MEK inhibition in pediatric B-lmphoblastic leukemia: a pilot study. American Society of Hematology Annual Meeting and Exhibition. Blood, San Diego, CA, 2016. 1739.
  • Mar BG, Bullinger LB, McLean KM, et al. Mutations in epigenetic regulators including SETD2 are gained during relapse in paediatric acute lymphoblastic leukaemia. Nat Commun. 2014;5:3469.
  • Mullighan CG, Zhang J, Kasper LH, et al. CREBBP mutations in relapsed acute lymphoblastic leukae mia. Nature. 2011;471(7337):235–239.
  • Jaffe JD, Wang Y, Chan HM, et al. Global chromatin profiling reveals NSD2 mutations in pediatric acute lymphoblastic leukemia. Nat Genet. 2013;45(11):1386–1391.
  • Inthal A, Zeitlhofer P, Zeginigg M, et al. CREBBP HAT domain mutations prevail in relapse cases of high hyperdiploid childhood acute lymphoblastic leukemia. Leukemia. 2012;26(8):1797–1803.
  • Malinowska-Ozdowy K, Frech C, Schönegger A, et al. KRAS and CREBBP mutations: a relapse-linked malicious liaison in childhood high hyperdiploid acute lymphoblastic leukemia. Leukemia. 2015;29(8):1656–1667.
  • Bhojwani D, Yang JJ, Pui CH. Biology of childhood acute lymphoblastic leukemia. Pediatr Clin North Am. 2015;62(1):47–60.
  • Tasian SK, Loh ML, Hunger SP. Childhood acute lymphoblastic leukemia: integrating genomics into therapy. Cancer. 2015;121(20):3577–3590.
  • Tasian SK, Hunger SP. Genomic characterization of paediatric acute lymphoblastic leukaemia: an opportunity for precision medicine therapeutics. Br J Haematol. 2017 Mar;176(6):867-882.
  • Roberts KG, Mullighan CG. How new advances in genetic analysis are influencing the understanding and treatment of childhood acute leukemia. Curr Opin Pediatr. 2011;23(1):34–40.
  • Reshmi SC, Harvey RC, Roberts KG, et al. Targetable kinase gene fusions in high risk B-ALL: a study from the Children’s Oncology Group. Blood. 2017.
  • Roberts KG, Li Y, Payne-Turner D, et al. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med. 2014;371(11):1005–1015.
  • Saliba J, Evensen NA, Meyer J et al. Using whole exome sequencing in pediatric acute lymphoblastic leukemia germline, diagnosis, and relapse trios to discover novel relapse enriched mutations for clonal backtracking by Ddpcr. American Society of Hematology Annual Meeting and Exhibition. Blood, San Diego, CA, 2016.
  • Troeger A, Siepermann M, Escherich G, et al. Survivin and its prognostic significance in pediatric acute B-cell precursor lymphoblastic leukemia. Haematologica. 2007;92(8):1043–1050.
  • Tyner JW, Jemal AM, Thayer M, et al. Targeting survivin and p53 in pediatric acute lymphoblastic leukemia. Leukemia. 2012;26(4):623–632.
  • Morrison DJ, Hogan LE, Condos G, et al. Endogenous knockdown of survivin improves chemotherapeutic response in ALL models. Leukemia. 2012;26(2):271–279.
  • Raetz EA, Morrison D, Romanos-Sirakis E, et al. A phase I study of EZN-3042, a novel survivin messenger ribonucleic acid (mRNA) antagonist, administered in combination with chemotherapy in children with relapsed acute lymphoblastic leukemia (ALL): a report from the therapeutic advances in childhood leukemia and lymphoma (TACL) consortium. J Pediatr Hematol Oncol. 2014;36(6):458–463.
  • McComb S, Aguadé-Gorgorió J, Harder L, et al. Activation of concurrent apoptosis and necroptosis by SMAC mimetics for the treatment of refractory and relapsed ALL. Sci Transl Med. 2016;8(339):339ra370.
  • Frismantas V, Dobay MP, Rinaldi A, et al. Ex vivo drug response profiling detects recurrent sensitivity patterns in drug-resistant acute lymphoblastic leukemia. Blood. 2017;129(11):e26–e37.
  • Khaw SL, Suryani S, Evans K, et al. Venetoclax responses of pediatric ALL xenografts reveal sensitivity of MLL-rearranged leukemia. Blood. 2016;128(10):1382–1395.
  • Case M, Matheson E, Minto L, et al. Mutation of genes affecting the RAS pathway is common in childhood acute lymphoblastic leukemia. Cancer Res. 2008;68(16):6803–6809.
  • Irving JA, Enshaei A, Parker CA, et al. Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukemia. Blood. 2016;128(7):911–922.
  • Polak A, Kiliszek P, Sewastianik T, et al. MEK inhibition sensitizes precursor B-cell acute lymphoblastic leukemia (B-ALL) cells to dexamethasone through modulation of mTOR activity and stimulation of autophagy. PLoS One. 2016;11(5):e0155893.
  • Bhatla T, Wang J, Morrison DJ, et al. Epigenetic reprogramming reverses the relapse-specific gene expression signature and restores chemosensitivity in childhood B-lymphoblastic leukemia. Blood. 2012;119(22):5201–5210.
  • Burke MJ, Lamba JK, Pounds S, et al. A therapeutic trial of decitabine and vorinostat in combination with chemotherapy for relapsed/refractory acute lymphoblastic leukemia. Am J Hematol. 2014;89(9):889–895.
  • Ribera JM, Ferrer A, Ribera J, et al. Profile of blinatumomab and its potential in the treatment of relapsed/refractory acute lymphoblastic leukemia. Onco Targets Ther. 2015;8:1567–1574.
  • Buie LW, Pecoraro JJ, Horvat TZ, et al. Blinatumomab: a first-in-class bispecific T-cell engager for precursor B-cell acute lymphoblastic leukemia. Ann Pharmacother. 2015;49(9):1057–1067.
  • Bargou R, Leo E, Zugmaier G, et al. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science. 2008;321(5891):974–977.
  • Topp MS, Kufer P, Gökbuget N, et al. Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol. 2011;29(18):2493–2498.
  • Topp MS, Gökbuget N, Zugmaier G, et al. Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. Blood. 2012;120(26):5185–5187.
  • Gökbuget N, Zugmaier G, Klinger M, et al. Long-term relapse-free survival in a phase 2 study of blinatumomab for the treatment of patients with minimal residual disease in B-lineage acute lymphoblastic leukemia. Haematologica. 2017.
  • Topp MS, Gökbuget N, Zugmaier G, et al. Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia. J Clin Oncol. 2014;32(36):4134–4140.
  • Topp MS, Gökbuget N, Stein AS, et al. 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. 2015;16(1):57–66.
  • Kantarjian H, Stein A, Gökbuget N, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376(9):836–847.
  • von Stackelberg A, Locatelli F, Zugmaier G, et al. Phase I/phase ii study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. J Clin Oncol. 2016;34(36):4381–4389.
  • Schlegel P, Lang P, Zugmaier G, et al. Pediatric posttransplant relapsed/refractory B-precursor acute lymphoblastic leukemia shows durable remission by therapy with the T-cell engaging bispecific antibody blinatumomab. Haematologica. 2014;99(7):1212–1219.
  • Piccaluga PP, Arpinati M, Candoni A, et al. Surface antigens analysis reveals significant expression of candidate targets for immunotherapy in adult acute lymphoid leukemia. Leuk Lymphoma. 2011;52(2):325–327.
  • Raetz EA, Cairo MS, Borowitz MJ, et al. Re-induction chemoimmunotherapy with epratuzumab in relapsed acute lymphoblastic leukemia (ALL): phase II results from Children’s Oncology Group (COG) study ADVL04P2. Pediatr Blood Cancer. 2015;62(7):1171–1175.
  • Irving JA. Towards an understanding of the biology and targeted treatment of paediatric relapsed acute lymphoblastic leukaemia. Br J Haematol. 2016;172(5):655–666.
  • Shor B, Gerber HP, Sapra P. Preclinical and clinical development of inotuzumab-ozogamicin in hematological malignancies. Mol Immunol. 2015;67(2 Pt A):107–116.
  • Thorson JS, Sievers EL, Ahlert J, et al. Understanding and exploiting nature’s chemical arsenal: the past, present and future of calicheamicin research. Curr Pharm Des. 2000;6(18):1841–1879.
  • Advani A, Coiffier B, Czuczman MS, et al. Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin’s lymphoma: results of a phase I study. J Clin Oncol. 2010;28(12):2085–2093.
  • Kantarjian H, Thomas D, Jorgensen J, et al. Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study. Lancet Oncol. 2012;13(4):403–411.
  • Kantarjian H, Thomas D, Jorgensen J, et al. Results of inotuzumab ozogamicin, a CD22 monoclonal antibody, in refractory and relapsed acute lymphocytic leukemia. Cancer. 2013;119(15):2728–2736.
  • DeAngelo DJ. The use of novel monoclonal antibodies in the treatment of acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program. 2015;2015:400–405.
  • Kantarjian HM, DeAngelo DJ, Stelljes M, et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med. 2016;375(8):740–753.
  • Rytting M, Triche L, Thomas D, et al. Initial experience with CMC-544 (inotuzumab ozogamicin) in pediatric patients with relapsed B-cell acute lymphoblastic leukemia. Pediatr Blood Cancer. 2014;61(2):369–372.
  • Advani AS, Moseley A, Liedtke M et al. A phase 1 trial of inotuzumab in combination with CVP (cyclophosphamide, vincristine, prednisone) for relapsed/refractory CD22+ acute Leukemia (SWOG 1312). American Society of Hematology Annual Meeting and Exposition. Blood, San Diego, CA, 2016.
  • Sasaki K, Jabbour EJ, O’Brien SM et al. Inotuzumab ozogamicin in combination with low-intensity chemotherapy (mini-hyper-CVD) as frontline therapy for older patients with Acute Lymphoblastic Leukemia (ALL): interim result of a phase ii clinical trial. American Society of Hematology Annual Meeting and Exposition. Blood, San Diego, CA, 2016.
  • Maude SL. Future directions in chimeric antigen receptor T cell therapy. Curr Opin Pediatr. 2017;29(1):27–33.
  • Huguet F, Tavitian S. Emerging biological therapies to treat acute lymphoblastic leukemia. Expert Opin Emerg Drugs. 2017 Mar;22(1):107-121.
  • Barrett DM, Singh N, Porter DL, et al. Chimeric antigen receptor therapy for cancer. Annu Rev Med. 2014;65:333–347.
  • Porter DL, Levine BL, Kalos M, et al. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011;365(8):725–733.
  • Grupp SA, Kalos M, Barrett D, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013;368(16):1509–1518.
  • Brentjens RJ, Davila ML, Riviere I, et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med. 2013;5(177):177ra138.
  • Maude SL, Frey N, Shaw PA, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371(16):1507–1517.
  • Maude SL, Teachey DT, Rheingold SR et al. Sustained remissions with CD19-specific chimeric antigen receptor (CAR)-modified T cells in children with relapsed/refractory ALL. 2016 ASCO Annual Meeting. Chicago, IL (J Clin Oncol, Chicago, IL), 2016.
  • Davila ML, Brentjens RJ. CD19-Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia. Clin Adv Hematol Oncol. 2016;14(10):802–808.
  • Park JH, Riviere I, Wang X, et al. Impact of disease burden on long-term outcome of 19-28z CAR modified T cells in adult patients with relapsed B-ALL. ASCO Annual Meeting; Chicago, IL. 2016.
  • Lee DW, Kochenderfer JN, Stetler-Stevenson M, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015;385(9967):517–528.
  • Morris EC, Stauss HJ. Optimizing T-cell receptor gene therapy for hematologic malignancies. Blood. 2016;127(26):3305–3311.
  • Qasim W, Zhan H, Samarasinghe S, et al. Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells. Sci Transl Med. 2017;9:374.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.