Skip to main content

Advertisement

SpringerLink
Log in

Novel Therapies for Older Adults With Acute Lymphoblastic Leukemia

  • Acute Lymphocytic Leukemias (K Ballen and M Keng, Section Editors)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Older adults with acute lymphoblastic leukemia (ALL) have worse survival compared to their younger counterparts. Here, we review the reasons for the poorer outcomes of older patients with ALL and also summarize the current and future therapeutic approaches to ALL in the elderly population.

Recent Findings

The poor outcomes of older adults with ALL are driven largely by lack of tolerance to standard-dose chemotherapy, which leads to unacceptably high rates of myelosuppression-related deaths. Recent studies have shown promising results with the use of low-intensity or chemotherapy-free regimens in older patients with ALL, which are able to retain efficacy without excess toxicity.

Summary

Novel antibody constructs such as inotuzumab ozogamicin and blinatumomab as well as potent later-generation tyrosine kinase inhibitors such as ponatinib hold significant promise in the management of ALL in the older adult. Innovative combination strategies may further improve the outcomes of these patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. National Cancer Institute. Cancer stat facts: acute lymphocytic leukemia (ALL). In: Surveillance, Epidemiology, and End Results Program. https://seer.cancer.gov/statfacts/html/alyl.html. Accessed 11/21/17 2017.

  2. Smith BD, Smith GL, Hurria A, Hortobagyi GN, Buchholz TA. Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol. 2009;27(17):2758–65. https://doi.org/10.1200/jco.2008.20.8983.

    Article  PubMed  Google Scholar 

  3. Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J Med. 2015;373(16):1541–52. https://doi.org/10.1056/NEJMra1400972.

    Article  CAS  PubMed  Google Scholar 

  4. •• Sive JI, Buck G, Fielding A, Lazarus HM, Litzow MR, Luger S, et al. Outcomes in older adults with acute lymphoblastic leukaemia (ALL): results from the international MRC UKALL XII/ECOG2993 trial. Br J Haematol. 2012;157(4):463–71. https://doi.org/10.1111/j.1365-2141.2012.09095.x. Showed worse outcomes for older adults compared to their younger counterparts and evaluated predictors for survival in the older population.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, et al. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014;123(6):843–50. https://doi.org/10.1182/blood-2013-09-529008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM, et al. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005;106(12):3760–7. https://doi.org/10.1182/blood-2005-04-1623.

    Article  CAS  PubMed  Google Scholar 

  7. Gokbuget N. How I treat older patients with ALL. Blood. 2013;122(8):1366–75. https://doi.org/10.1182/blood-2012-07-379016.

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1002/cncr.23819. Showed worse outcomes for older patients treated with the intensive hyper-CVAD regimen, driven largely by myelosuppression-related deaths.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Geyer MB, Hsu M, Devlin SM, Tallman MS, Douer D, Park JH. Overall survival among older US adults with ALL remains low despite modest improvement since 1980: SEER analysis. Blood. 2017;129(13):1878–81. https://doi.org/10.1182/blood-2016-11-749507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Li S, Molony JT, Chia V, Katz AJ. Patient characteristics and treatment patterns in elderly patients newly diagnosed with acute lymphoblastic leukemia (ALL) using 100% medicare ALL data. Blood. 2016;128(22):3981.

    Google Scholar 

  11. Saillard C, Etienne A, Charbonnier A, D'Incan E, Rey J, Arnoulet C, et al. Evaluation of comorbidity indexes in the outcome of elderly patients treated for acute lymphoblastic leukemia. Leuk Lymphoma. 2014;55(9):2211–2. https://doi.org/10.3109/10428194.2013.876497.

    Article  PubMed  Google Scholar 

  12. Lees J, Chan A. Polypharmacy in elderly patients with cancer: clinical implications and management. Lancet Oncol. 2011;12(13):1249–57. https://doi.org/10.1016/s1470-2045(11)70040-7.

    Article  PubMed  Google Scholar 

  13. Elliot K, Tooze JA, Geller R, Powell BL, Pardee TS, Ritchie E, et al. The prognostic importance of polypharmacy in older adults treated for acute myelogenous leukemia (AML). Leuk Res. 2014;38(10):1184–90. https://doi.org/10.1016/j.leukres.2014.06.018.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Thomas X, Olteanu N, Charrin C, Lheritier V, Magaud JP, Fiere D. Acute lymphoblastic leukemia in the elderly: the Edouard Herriot Hospital experience. Am J Hematol. 2001;67(2):73–83. https://doi.org/10.1002/ajh.1083.

    Article  CAS  PubMed  Google Scholar 

  15. Issa GC, Kantarjian HM, Yin CC, Qiao W, Ravandi F, Thomas D, et al. Prognostic impact of pretreatment cytogenetics in adult Philadelphia chromosome-negative acute lymphoblastic leukemia in the era of minimal residual disease. Cancer. 2016;123(3):459–67. https://doi.org/10.1002/cncr.30376.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Moorman AV, Chilton L, Wilkinson J, Ensor HM, Bown N, Proctor SJ. A population-based cytogenetic study of adults with acute lymphoblastic leukemia. Blood. 2010;115(2):206–14. https://doi.org/10.1182/blood-2009-07-232124.

    Article  CAS  PubMed  Google Scholar 

  17. Moorman AV, Harrison CJ, Buck GA, Richards SM, Secker-Walker LM, Martineau M, et al. Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood. 2007;109(8):3189–97. https://doi.org/10.1182/blood-2006-10-051912.

    Article  CAS  PubMed  Google Scholar 

  18. Igwe IJ, Yang D, Merchant A, Merin N, Yaghmour G, Kelly K, et al. The presence of Philadelphia chromosome does not confer poor prognosis in adult pre-B acute lymphoblastic leukaemia in the tyrosine kinase inhibitor era—a surveillance, epidemiology, and end results database analysis. Br J Haematol. 2017;179(4):618–26. https://doi.org/10.1111/bjh.14953.

    Article  CAS  PubMed  Google Scholar 

  19. Byun JM, Koh Y, Shin DY, Kim I, Yoon SS, Lee JO, et al. BCR-ABL translocation as a favorable prognostic factor in elderly patients with acute lymphoblastic leukemia in the era of potent tyrosine kinase inhibitors. Haematologica. 2017;102(5):e187–e90. https://doi.org/10.3324/haematol.2016.159988.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Kanagal-Shamanna R, Jain P, Takahashi K, Short NJ, Tang G, Issa GC, et al. TP53 mutation does not confer a poor outcome in adult patients with acute lymphoblastic leukemia who are treated with frontline hyper-CVAD-based regimens. Cancer. 2017;123(19):3717–24. https://doi.org/10.1002/cncr.30810.

    Article  CAS  PubMed  Google Scholar 

  21. Stengel A, Kern W, Haferlach T, Meggendorfer M, Fasan A, Haferlach C. The impact of TP53 mutations and TP53 deletions on survival varies between AML, ALL, MDS and CLL: an analysis of 3307 cases. Leukemia. 2017;31(3):705–11. https://doi.org/10.1038/leu.2016.263.

    CAS  PubMed  Google Scholar 

  22. Ribera J, Morgades M, Zamora L, Montesinos P, Gomez-Segui I, Pratcorona M, et al. Prognostic significance of copy number alterations in adolescent and adult patients with precursor B acute lymphoblastic leukemia enrolled in PETHEMA protocols. Cancer. 2015;121(21):3809–17. https://doi.org/10.1002/cncr.29579.

    Article  CAS  PubMed  Google Scholar 

  23. Beldjord K, Chevret S, Asnafi V, Huguet F, Boulland ML, Leguay T, et al. Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia. Blood. 2014;123(24):3739–49. https://doi.org/10.1182/blood-2014-01-547695.

    Article  CAS  PubMed  Google Scholar 

  24. Martinelli G, Iacobucci I, Storlazzi CT, Vignetti M, Paoloni F, Cilloni D, et al. IKZF1 (Ikaros) deletions in BCR-ABL1-positive acute lymphoblastic leukemia are associated with short disease-free survival and high rate of cumulative incidence of relapse: a GIMEMA AL WP report. J Clin Oncol. 2009;27(31):5202–7. https://doi.org/10.1200/jco.2008.21.6408.

    Article  CAS  PubMed  Google Scholar 

  25. DeBoer R, Koval G, Mulkey F, Wetzler M, Devine S, Marcucci G, et al. Clinical impact of ABL1 kinase domain mutations and IKZF1 deletion in adults under age 60 with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL): molecular analysis of CALGB (Alliance) 10001 and 9665. Leuk Lymphoma. 2016;57(10):2298–306. https://doi.org/10.3109/10428194.2016.1144881.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sancho JM, Ribera JM, Xicoy B, Morgades M, Oriol A, Tormo M, et al. Results of the PETHEMA ALL-96 trial in elderly patients with Philadelphia chromosome-negative acute lymphoblastic leukemia. Eur J Haematol. 2007;78(2):102–10. https://doi.org/10.1111/j.1600-0609.2006.00778.x.

    CAS  PubMed  Google Scholar 

  27. Goekbuget N, Leguay T, Hunault M, Al-Nawakil C, Chevallier P, Dombret H, et al. First European chemotherapy schedule for elderly patients with acute lymphoblastic leukemia: promising remission rate and feasible moderate dose intensity consolidation. Blood. 2008;112(11):304.

    Google Scholar 

  28. Hunault-Berger M, Leguay T, Thomas X, Legrand O, Huguet F, Bonmati C, et al. A randomized study of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in elderly patients with acute lymphoblastic leukemia: the GRAALL-SA1 study. Haematologica. 2011;96(2):245–52. https://doi.org/10.3324/haematol.2010.027862.

    Article  CAS  PubMed  Google Scholar 

  29. •• Goekbuget N, Beck J, Brueggemann M, Burmeister T, Buss EC, Frickhofen N, et al. Moderate intensive chemotherapy including CNS-prophylaxis with liposomal cytarabine is feasible and effective in older patients with Ph-negative acute lymphoblastic leukemia (ALL): results of a prospective trial from the German multicenter study Group for Adult ALL (GMALL). Blood. 2012;120(21):1493. Largest prospective study of older patients with Ph-negative ALL.

    Google Scholar 

  30. Ribera JM, Garcia O, Oriol A, Gil C, Montesinos P, Bernal T, et al. Feasibility and results of subtype-oriented protocols in older adults and fit elderly patients with acute lymphoblastic leukemia: results of three prospective parallel trials from the PETHEMA group. Leuk Res. 2016;41:12–20. https://doi.org/10.1016/j.leukres.2015.11.012.

    Article  PubMed  Google Scholar 

  31. •• Kantarjian H, Ravandi F, Short NJ, Huang X, Jain N. Inotuzumab ozogamicin in combination with low-intensity chemotherapy (mini-hyper-CVD) as frontline therapy for older patients with Philadelphia chromosome-negative acute lymphoblastic leukemia: a single-arm, phase II study. Lancet Oncol. 2018 Jan 15. pii: S1470-2045(18)30011-1. doi: https://doi.org/10.1016/S1470-2045(18)30011-1. [Epub ahead of print] Showed high efficacy and promising long-term survival using novel agent (i.e. inotuzumab ozagamicin) in combination with low-intensity chemotherapy for elderly ALL.

  32. Thomas DA, O'Brien S, Jorgensen JL, Cortes J, Faderl S, Garcia-Manero G, et al. Prognostic significance of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia. Blood. 2009;113(25):6330–7. https://doi.org/10.1182/blood-2008-04-151860.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Maury S, Chevret S, Thomas X, Heim D, Leguay T, Huguet F, et al. Rituximab in B-lineage adult acute lymphoblastic leukemia. N Engl J Med. 2016;375(11):1044–53. https://doi.org/10.1056/NEJMoa1605085.

    Article  CAS  PubMed  Google Scholar 

  34. Kantarjian HM, DeAngelo DJ, Stelljes M, Martinelli G, Liedtke M, Stock W, et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med. 2016;375(8):740–53. https://doi.org/10.1056/NEJMoa1509277.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Jabbour E, Advani AS, Stelljes M, Stock W, Liedtke M, Gökbuget N, et al. Efficacy and safety of inotuzumab ozogamicin (InO) in older patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) enrolled in the phase 3 INO-VATE trial. J Clin Oncol. 2016;34(15_suppl):7029. https://doi.org/10.1200/JCO.2016.34.15_suppl.7029.

    Google Scholar 

  36. Short NJ, Kantarjian H, Jabbour E, Ravandi F. Which tyrosine kinase inhibitor should we use to treat Philadelphia chromosome-positive acute lymphoblastic leukemia? Best Pract Res Clin Haematol. 2017;30(3):193–200. https://doi.org/10.1016/j.beha.2017.05.001.

    Article  PubMed  Google Scholar 

  37. Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, et al. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993. Blood. 2009;113(19):4489–96. https://doi.org/10.1182/blood-2009-01-199380.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Daver N, Thomas D, Ravandi F, Cortes J, Garris R, Jabbour E, et al. Final report of a phase II study of imatinib mesylate with hyper-CVAD for the front-line treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Haematologica. 2015;100(5):653–61. https://doi.org/10.3324/haematol.2014.118588.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Chalandon Y, Thomas X, Hayette S, Cayuela JM, Abbal C, Huguet F, et al. Randomized study of reduced-intensity chemotherapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia. Blood. 2015;125(24):3711–9. https://doi.org/10.1182/blood-2015-02-627935.

    Article  CAS  PubMed  Google Scholar 

  40. Ravandi F, O'Brien SM, Cortes JE, Thomas DM, Garris R, Faderl S, et al. Long-term follow-up of a phase 2 study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer. 2015;121(23):4158–64. https://doi.org/10.1002/cncr.29646.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kim DY, Joo YD, Lim SN, Kim SD, Lee JH, Lee JH, et al. Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Blood. 2015;126(6):746–56. https://doi.org/10.1182/blood-2015-03-636548.

    Article  CAS  PubMed  Google Scholar 

  42. Jabbour E, Kantarjian H, Ravandi F, Thomas D, Huang X, Faderl S, et al. Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: a single-centre, phase 2 study. Lancet Oncol. 2015;16(15):1547–55. https://doi.org/10.1016/s1470-2045(15)00207-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ravandi F, Jorgensen JL, Thomas DA, O'Brien S, Garris R, Faderl S, et al. Detection of MRD may predict the outcome of patients with Philadelphia chromosome-positive ALL treated with tyrosine kinase inhibitors plus chemotherapy. Blood. 2013;122(7):1214–21. https://doi.org/10.1182/blood-2012-11-466482.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Short NJ, Jabbour E, Sasaki K, Patel K, O'Brien SM, Cortes JE, et al. Impact of complete molecular response on survival in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2016;128(4):504–7. https://doi.org/10.1182/blood-2016-03-707562.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Short NJ, Kantarjian HM, Ravandi F, Daver NG, Pemmaraju N, Thomas DA, et al. Frontline hyper-CVAD plus ponatinib for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: Updated results of a phase II study. J Clin Oncol. 2017;35(15_suppl):7013. https://doi.org/10.1200/JCO.2017.35.15_suppl.7013.

    Google Scholar 

  46. Sasaki K, Jabbour EJ, Ravandi F, Short NJ, Thomas DA, Garcia-Manero G, et al. Hyper-CVAD plus ponatinib versus hyper-CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: a propensity score analysis. Cancer. 2016;122(23):3650–6. https://doi.org/10.1002/cncr.30231.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Dorer DJ, Knickerbocker RK, Baccarani M, Cortes JE, Hochhaus A, Talpaz M, et al. Impact of dose intensity of ponatinib on selected adverse events: multivariate analyses from a pooled population of clinical trial patients. Leuk Res. 2016;48:84–91. https://doi.org/10.1016/j.leukres.2016.07.007.

    Article  CAS  PubMed  Google Scholar 

  48. Vignetti M, Fazi P, Cimino G, Martinelli G, Di Raimondo F, Ferrara F, et al. Imatinib plus steroids induces complete remissions and prolonged survival in elderly Philadelphia chromosome-positive patients with acute lymphoblastic leukemia without additional chemotherapy: results of the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) LAL0201-B protocol. Blood. 2007;109(9):3676–8. https://doi.org/10.1182/blood-2006-10-052746.

    Article  CAS  PubMed  Google Scholar 

  49. Ottmann OG, Pfeifer H, Cayuela J-M, Spiekermann K, Beck J, Jung WE, et al. Nilotinib (Tasigna®) and Chemotherapy for First-Line Treatment in Elderly Patients with <em>De Novo</em> Philadelphia Chromosome/BCR-ABL1 Positive Acute Lymphoblastic Leukemia (ALL): A Trial of the European Working Group for Adult ALL (EWALL-PH-02). Blood. 2014;124(21):798.

    Google Scholar 

  50. •• Rousselot P, Coude MM, Gokbuget N, Gambacorti Passerini C, Hayette S, Cayuela JM, et al. Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome-positive ALL. Blood. 2016;128(6):774–82. https://doi.org/10.1182/blood-2016-02-700153. Showed feasability of TKI with low-intensity chemotherapy in older Ph-positive ALL. Also notable for high rate of T315I mutations at relapse.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Foa R, Vitale A, Vignetti M, Meloni G, Guarini A, De Propris MS, et al. Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2011;118(25):6521–8. https://doi.org/10.1182/blood-2011-05-351403.

    Article  CAS  PubMed  Google Scholar 

  52. Martinelli G, Piciocchi A, Papayannidis C, Paolini S, V R, Soverini S et al. First report of the Gimema LAL1811 Phase II Prospective Study of the combination of steroids with ponatinib as frontline therapy of elderly or unfit patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2017.

  53. Speziali C, Paulson K, Seftel M. Hematopoietic cell transplantation for acute lymphoblastic leukemia in adults. Curr Hematol Malig Rep. 2016;11(3):175–84. https://doi.org/10.1007/s11899-016-0317-2.

    Article  PubMed  Google Scholar 

  54. Elsawy M, Sorror ML. Up-to-date tools for risk assessment before allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2016;51(10):1283–300. https://doi.org/10.1038/bmt.2016.141.

    Article  CAS  PubMed  Google Scholar 

  55. Muffly LS, Kocherginsky M, Stock W, Chu Q, Bishop MR, Godley LA, et al. Geriatric assessment to predict survival in older allogeneic hematopoietic cell transplantation recipients. Haematologica. 2014;99(8):1373–9. https://doi.org/10.3324/haematol.2014.103655.

    Article  PubMed  PubMed Central  Google Scholar 

  56. • Mohty M, Labopin M, Volin L, Gratwohl A, Socie G, Esteve J, et al. Reduced-intensity versus conventional myeloablative conditioning allogeneic stem cell transplantation for patients with acute lymphoblastic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation. Blood. 2010;116(22):4439–43. https://doi.org/10.1182/blood-2010-02-266551. Large study of older adults who underwent allogeneic stem cell transplantation for ALL.

    Article  CAS  PubMed  Google Scholar 

  57. Rosko A, Wang HL, de Lima M, Sandmaier B, Khoury HJ, Artz A, et al. Reduced intensity conditioned allograft yields favorable survival for older adults with B-cell acute lymphoblastic leukemia. Am J Hematol. 2017;92(1):42–9. https://doi.org/10.1002/ajh.24575.

    Article  CAS  PubMed  Google Scholar 

  58. Kantarjian H, Stein A, Gokbuget N, Fielding AK, Schuh AC, Ribera JM, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376(9):836–47. https://doi.org/10.1056/NEJMoa1609783.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kantarjian HM, Stein AS, Bargou RC, Grande Garcia C, Larson RA, Stelljes M, et al. Blinatumomab treatment of older adults with relapsed/refractory B-precursor acute lymphoblastic leukemia: results from 2 phase 2 studies. Cancer. 2016;122(14):2178–85. https://doi.org/10.1002/cncr.30031.

    Article  CAS  PubMed  Google Scholar 

  60. Assi R, Kantarjian H, Short NJ, Daver N, Takahashi K, Garcia-Manero G, et al. Safety and efficacy of blinatumomab in combination with a tyrosine kinase inhibitor for the treatment of relapsed Philadelphia chromosome-positive leukemia. Clin Lymphoma Myeloma Leuk. 2017;17(12):897–901. https://doi.org/10.1016/j.clml.2017.08.101.

    Article  PubMed  Google Scholar 

  61. Roberts AW, Davids MS, Pagel JM, Kahl BS, Puvvada SD, Gerecitano JF, et al. Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016;374(4):311–22. https://doi.org/10.1056/NEJMoa1513257.

    Article  CAS  PubMed  Google Scholar 

  62. Wei A, Strickland SA, Roboz GJ, Hou J-Z, Fiedler W, Lin TL, et al. Safety and efficacy of venetoclax plus low-dose cytarabine in treatment-naive patients aged ≥65 years with acute myeloid leukemia. Blood. 2016;128(22):102.

    Google Scholar 

  63. Pollyea DA, Dinardo CD, Thirman MJ, Letai A, Wei AH, Jonas BA, et al. Results of a phase 1b study of venetoclax plus decitabine or azacitidine in untreated acute myeloid leukemia patients ≥ 65 years ineligible for standard induction therapy. J Clin Oncol. 2016;34(15_suppl):7009. https://doi.org/10.1200/JCO.2016.34.15_suppl.7009.

    Google Scholar 

  64. Scherr M, Elder A, Battmer K, Barzan D, Bomken S. Differential expression of miR-17~92 identifies BCL2 as a therapeutic target in BCR-ABL-positive B-lineage acute lymphoblastic leukemia. Leukemia. 2014;28(3):554–65. https://doi.org/10.1038/leu.2013.361.

    Article  CAS  PubMed  Google Scholar 

  65. Alford SE, Kothari A, Loeff FC, Eichhorn JM, Sakurikar N, Goselink HM, et al. BH3 inhibitor sensitivity and Bcl-2 dependence in primary acute lymphoblastic leukemia cells. Cancer Res. 2015;75(7):1366–75. https://doi.org/10.1158/0008-5472.can-14-1849.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Leonard JT, Rowley JS, Eide CA, Traer E, Hayes-Lattin B, Loriaux M, et al. Targeting BCL-2 and ABL/LYN in Philadelphia chromosome-positive acute lymphoblastic leukemia. Sci Transl Med. 2016;8(354):354ra114. https://doi.org/10.1126/scitranslmed.aaf5309.

    Article  PubMed  Google Scholar 

  67. Jabbour E, Ravandi F, Kebriaei P, Huang X, Short NJ, Thomas D, Sasaki K, Rytting M, Jain N, Konopleva M, Garcia-Manero G, Champlin R, Marin D, Kadia T, Cortes J, Estrov Z, Takahashi K, Patel Y, Khouri MR, Jacob J, Garris R, O’Brien S, Kantarjian H. Salvage chemoimmunotherapy with inotuzumab ozogamicin combined with mini-hyper-CVD for patients with relapsed or refractory Philadelphia chromosome-negative acute lymphoblastic leukemia: a phase 2 clinical trial. JAMA Oncol 2017. https://doi.org/10.1001/jamaoncol.2017.2380.

Download references

Funding

This study was supported by the MD Anderson Cancer Center Support Grant CA016672.

Author information

Authors and Affiliations

  1. Department of Leukemia, Unit 428, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA

    Nicholas J. Short, Hagop Kantarjian, Elias Jabbour & Farhad Ravandi

Authors
  1. Nicholas J. Short
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hagop Kantarjian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elias Jabbour
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Farhad Ravandi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Farhad Ravandi.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Acute Lymphocytic Leukemias

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Short, N.J., Kantarjian, H., Jabbour, E. et al. Novel Therapies for Older Adults With Acute Lymphoblastic Leukemia. Curr Hematol Malig Rep 13, 91–99 (2018). https://doi.org/10.1007/s11899-018-0440-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11899-018-0440-3

Keywords

Search

Navigation