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Kantarjian HM, Jain N, Garcia-Manero G, et al. The cure of leukemia through the optimist's prism. Cancer. 2021;doi: 10.1002/cncr.33933.
Kantarjian, H. M., Jain, N., Garcia-Manero, G., Welch, M. A., Ravandi, F., Wierda, W. G., & Jabbour, E. J. (2021). The cure of leukemia through the optimist's prism. Cancer, . https://doi.org/10.1002/cncr.33933
Kantarjian, Hagop M, et al. "The cure of leukemia through the optimist's prism." Cancer vol. (2021). doi: https://doi.org/10.1002/cncr.33933
Kantarjian HM, Jain N, Garcia-Manero G, Welch MA, Ravandi F, Wierda WG, Jabbour EJ. The cure of leukemia through the optimist's prism. Cancer. 2021 Oct 06; doi: 10.1002/cncr.33933. Epub 2021 Oct 06. PMID: 34614211.
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Cancer. 2021 Oct 06; doi: 10.1002/cncr.33933. Epub 2021 Oct 06.

The cure of leukemia through the optimist's prism.

Cancer

Hagop M Kantarjian, Nitin Jain, Guillermo Garcia-Manero, Mary Alma Welch, Farhad Ravandi, William G Wierda, Elias J Jabbour

Affiliations

  1. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.

PMID: 34614211 DOI: 10.1002/cncr.33933

Abstract

Progress is occurring at a dizzying rate across all leukemias. Since the authors' review of the topic in Cancer in 2018, numerous discoveries have been made that have improved the therapy and outcomes of several leukemia subsets. Hairy cell leukemia is potentially curable with a single course of cladribine followed by rituximab (10-year survival, ≥90%). Acute promyelocytic leukemia is curable at a rate of 80% to 90% with a nonchemotherapy regimen of all-trans retinoic acid and arsenic trioxide. The cure rate for core-binding factor acute myeloid leukemia (AML) is ≥75% with fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin. Survival for patients with chronic myeloid leukemia is close to that for an age-matched normal population with BCR-ABL1 tyrosine kinase inhibitors (TKIs). Chronic lymphocytic leukemia, a previously incurable disease, may now be potentially curable with a finite duration of therapy with Bruton tyrosine kinase inhibitors and venetoclax. The estimated 5-year survival rate for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) exceeds 70% with intensive chemotherapy and ponatinib, a third-generation BCR-ABL1 TKI, and more recent nonchemotherapy regimens using dasatinib or ponatinib with blinatumomab are producing outstanding results. Survival in both younger and older patients with ALL has improved with the addition of antibodies targeting CD20, CD19 (blinatumomab), and CD22 (inotuzumab) to chemotherapy. Several recent drug discoveries (venetoclax, FLT3 and IDH inhibitors, and oral hypomethylating agents) are also improving outcomes for younger and older patients with AML and for those with higher risk myelodysplastic syndrome.

© 2021 American Cancer Society.

Keywords: leukemia; prognosis; progress; therapy; updates

References

  1. Freireich EJ, Wiernik PH, Steensma DP. The leukemias: a half-century of discovery. J Clin Oncol. 2014;32:3463-3469. - PubMed
  2. Kantarjian HM, Keating MJ, Freireich EJ. Toward the potential cure of leukemias in the next decade. Cancer. 2018;124:4301-4313. - PubMed
  3. Jain N, Keating M, Thompson P, et al. Ibrutinib and venetoclax for first-line treatment of CLL. N Engl J Med. 2019;380:2095-2103. - PubMed
  4. Jain N, Keating M, Thompson P, et al. Ibrutinib plus venetoclax for first-line treatment of chronic lymphocytic leukemia: a nonrandomized phase 2 trial. JAMA Oncol. 2021;7:1213-1219. - PubMed
  5. Jabbour E, Short NJ, Ravandi F, et al. Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: long-term follow-up of a single-centre, phase 2 study. Lancet Haematol. 2018;5:e618-e627. - PubMed
  6. Foà R, Bassan R, Vitale A, et al. Dasatinib-blinatumomab for Ph-positive acute lymphoblastic leukemia in adults. N Engl J Med. 2020;383:1613-1623. - PubMed
  7. DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383:617-629. - PubMed
  8. Wei AH, Döhner H, Pocock C, et al. Oral azacitidine maintenance therapy for acute myeloid leukemia in first remission. N Engl J Med. 2020;383:2526-2537. - PubMed
  9. Grever MR, Abdel-Wahab O, Andritsos LA, et al. Consensus guidelines for the diagnosis and management of patients with classic hairy cell leukemia. Blood. 2017;129:553-560. - PubMed
  10. Rosenberg JD, Burian C, Waalen J, Saven A. Clinical characteristics and long-term outcome of young hairy cell leukemia patients treated with cladribine: a single-institution series. Blood. 2014;123:177-183. - PubMed
  11. Else M, Ruchlemer R, Osuji N, et al. Long remissions in hairy cell leukemia with purine analogs: a report of 219 patients with a median follow-up of 12.5 years. Cancer. 2005;104:2442-2448. - PubMed
  12. Thomas DA, O'Brien S, Bueso-Ramos C, et al. Rituximab in relapsed or refractory hairy cell leukemia. Blood. 2003;102:3906-3911. - PubMed
  13. Ravandi F, O'Brien S, Jorgensen J, et al. Phase 2 study of cladribine followed by rituximab in patients with hairy cell leukemia. Blood. 2011;118:3818-3823. - PubMed
  14. Chihara D, Kantarjian H, O'Brien S, et al. Long-term durable remission by cladribine followed by rituximab in patients with hairy cell leukaemia: update of a phase II trial. Br J Haematol. 2016;174:760-766. - PubMed
  15. Chihara D, Arons E, Stetler-Stevenson M, et al. Randomized phase II study of first-line cladribine with concurrent or delayed rituximab in patients with hairy cell leukemia. J Clin Oncol. 2020;38:1527-1538. doi:10.1200/JCO.19.02250 - PubMed
  16. Tiacci E, De Carolis L, Simonetti E, et al. Vemurafenib plus rituximab in refractory or relapsed hairy-cell leukemia. N Engl J Med. 2021;384:1810-1823. doi:10.1056/NEJMoa2031298 - PubMed
  17. de The H, Chen Z. Acute promyelocytic leukaemia: novel insights into the mechanisms of cure. Nat Rev Cancer. 2010;10:775-783. - PubMed
  18. Sanz MA, Grimwade D, Tallman MS, et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2009;113:1875-1891. - PubMed
  19. Bernard J, Weil M, Boiron M, et al. Acute promyelocytic leukemia: results of treatment by daunorubicin. Blood. 1973;41:489-496. - PubMed
  20. Kantarjian H, Kadia T, DiNardo C, et al. Acute myeloid leukemia: current progress and future directions. Blood Cancer J. 2021;11:41. - PubMed
  21. Kantarjian HM, Kadia TM, DiNardo CD, Welch MA, Ravandi F. Acute myeloid leukemia: treatment and research outlook for 2021 and the MD Anderson approach. Cancer. 2021;127:1186-1207. - PubMed
  22. Huang ME, Ye YC, Chen SR, et al. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988;72:567-572. - PubMed
  23. Shen Z-X, Chen G-Q, Ni J-H, et al. Use of arsenic trioxide (AS2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood. 1997;89:3354-3360. - PubMed
  24. Avvisati G, Lo-Coco F, Paoloni FP, et al. AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance. Blood. 2011;117:4716-4725. - PubMed
  25. Ghavamzadeh A, Alimoghaddam K, Rostami S, et al. Phase II study of single-agent arsenic trioxide for the front-line therapy of acute promyelocytic leukemia. J Clin Oncol. 2011;29:2753-2757. - PubMed
  26. Mathews V, George B, Chendamarai E, et al. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: long-term follow-up data. J Clin Oncol. 2010;28:3866-3871. - PubMed
  27. Estey EH, Giles FJ, Beran M, et al. Experience with gemtuzumab ozogamycin ("mylotarg") and all-trans retinoic acid in untreated acute promyelocytic leukemia. Blood. 2002;99:4222-4224. - PubMed
  28. Estey E, Garcia-Manero G, Ferrajoli A, et al. Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. Blood. 2006;107:3469-3473. - PubMed
  29. Ravandi F, Estey E, Jones D, et al. Effective treatment of acute promyelocytic leukemia with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin. J Clin Oncol. 2009;27:504-510. - PubMed
  30. Abaza Y, Kantarjian H, Garcia-Manero G, et al. Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab. Blood. 2017;129:1275-1283. - PubMed
  31. Lo-Coco F, Avvisati G, Vignetti M, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013;369:111-121. - PubMed
  32. Platzbecker U, Avvisati G, Cicconi L, et al. Improved outcomes with retinoic acid and arsenic trioxide compared with retinoic acid and chemotherapy in non-high-risk acute promyelocytic leukemia: final results of the randomized Italian-German APL0406 trial. J Clin Oncol. 2017;35:605-612. - PubMed
  33. Burnett AK, Russell NH, Hills RK, et al. Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2015;16:1295-1305. - PubMed
  34. Au WY, Kumana CR, Lee HK, et al. Oral arsenic trioxide-based maintenance regimens for first complete remission of acute promyelocytic leukemia: a 10-year follow-up study. Blood. 2011;118:6535-6543. - PubMed
  35. Zhu HH, Wu DP, Jin J, et al. Oral tetra-arsenic tetra-sulfide formula versus intravenous arsenic trioxide as first-line treatment of acute promyelocytic leukemia: a multicenter randomized controlled trial. J Clin Oncol. 2013;31:4215-4221. - PubMed
  36. Grimwade D, Jovanovic JV, Hills RK, et al. Prospective minimal residual disease monitoring to predict relapse of acute promyelocytic leukemia and to direct pre-emptive arsenic trioxide therapy. J Clin Oncol. 2009;27:3650-3658. - PubMed
  37. Marcucci G, Mrozek K, Ruppert AS, et al. Prognostic factors and outcome of core binding factor acute myeloid leukemia patients with t(8;21) differ from those of patients with inv(16): a Cancer and Leukemia Group B study. J Clin Oncol. 2005;23:5705-5717. - PubMed
  38. Appelbaum FR, Kopecky KJ, Tallman MS, et al. The clinical spectrum of adult acute myeloid leukaemia associated with core binding factor translocations. Br J Haematol. 2006;135:165-173. - PubMed
  39. Hills RK, Castaigne S, Appelbaum FR, et al. Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: a meta-analysis of individual patient data from randomised controlled trials. Lancet Oncol. 2014;15:986-996. - PubMed
  40. Borthakur G, Kantarjian H, Wang X, et al. Treatment of core-binding-factor in acute myelogenous leukemia with fludarabine, cytarabine, and granulocyte colony-stimulating factor results in improved event-free survival. Cancer. 2008;113:3181-3185. - PubMed
  41. Burnett AK, Hills RK, Milligan D, et al. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011;29:369-377. - PubMed
  42. Borthakur G, Cortes JE, Estey EE, et al. Gemtuzumab ozogamicin with fludarabine, cytarabine, and granulocyte colony stimulating factor (FLAG-GO) as front-line regimen in patients with core binding factor acute myelogenous leukemia. Am J Hematol. 2014;89:964-968. - PubMed
  43. Yin JA, O'Brien MA, Hills RK, Daly SB, Wheatley K, Burnett AK. Minimal residual disease monitoring by quantitative RT-PCR in core binding factor AML allows risk stratification and predicts relapse: results of the United Kingdom MRC AML-15 trial. Blood. 2012;120:2826-2835. - PubMed
  44. Ragon BK, Daver N, Garcia-Manero G, et al. Minimal residual disease eradication with epigenetic therapy in core binding factor acute myeloid leukemia. Am J Hematol. 2017;92:845-850. - PubMed
  45. Paschka P, Marcucci G, Ruppert AS, et al. Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): a Cancer and Leukemia Group B Study. J Clin Oncol. 2006;24:3904-3911. - PubMed
  46. Boissel N, Leroy H, Brethon B, et al. Incidence and prognostic impact of c-Kit, FLT3, and Ras gene mutations in core binding factor acute myeloid leukemia (CBF-AML). Leukemia. 2006;20:965-970. - PubMed
  47. Kantarjian H, Cortes J. Chronic myeloid leukemia. In: Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J, eds. Harrison's Principles of Internal Medicine, 20e. McGraw-Hill; 2018:748-757. - PubMed
  48. Kantarjian H, Cortes J, Jabbour E, O’Brien S. Chronic myeloid leukemia. In: Provan D, Gribben JG, eds. Molecular Hematology. 4th ed. Wiley-Blackwell; 2020:71-86. - PubMed
  49. Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2020 update on diagnosis, therapy and monitoring. Am J Hematol. 2020;95:691-709. - PubMed
  50. Sasaki K, Jabbour E, Cortes J, Kantarjian H. Chronic myeloid leukemia. In: Kantarjian HM, Wolff RA, eds. The MD Anderson Manual of Medical Oncology. McGraw-Hill; 2021:chap 4. - PubMed
  51. Hochhaus A, Larson RA, Guilhot F, et al. Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med. 2017;376:917-927. - PubMed
  52. Hehlmann R, Lauseker M, Saußele S, et al. Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants. Leukemia. 2017;31:2398-2406. - PubMed
  53. Sasaki K, Strom SS, O'Brien S, et al. Relative survival in patients with chronic-phase chronic myeloid leukaemia in the tyrosine-kinase inhibitor era: analysis of patient data from six prospective clinical trials. Lancet Haematol. 2015;2:e186-e193. - PubMed
  54. Kantarjian H, Hughes T, Larson RA, et al. Long-term outcomes with frontline nilotinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase: ENESTnd 10-year analysis. Leukemia. 2021;35:440-453. - PubMed
  55. Cortes JE, Saglio G, Kantarjian HM, et al. Final 5-year study results of DASISION: the dasatinib versus imatinib study in treatment-naïve chronic myeloid leukemia patients trial. J Clin Oncol. 2016;34:2333-2340. - PubMed
  56. Brummendorf T, Cortes J, Milojkovic D, et al. Bosutinib (BOS) versus imatinib for newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML): final 5-year results from the Bfore trial. Blood. 2020;136:46. - PubMed
  57. Cortes JE, Kim DW, Pinilla-Ibarz J, et al. Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial. Blood. 2018;132:393-404. - PubMed
  58. Naqvi K, Jabbour E, Skinner J, et al. Long-term follow-up of lower dose dasatinib (50 mg daily) as frontline therapy in newly diagnosed chronic-phase chronic myeloid leukemia. Cancer. 2020;126:67-75. - PubMed
  59. Cortes J, Apperley J, Hochhaus A, et al. Outcome by mutation status and line of treatment in Optic, a dose-ranging study of 3 starting doses of ponatinib in patients with CP-CML. Blood. 2020;136(suppl 1):44-45. - PubMed
  60. Kantarjian H, Deininger M, Abruzzese E, et al. Efficacy and safety of ponatinib (PON) in patients with chronic-phase chronic myeloid leukemia (CP-CML) who failed one or more second-generation (2G) tyrosine kinase inhibitors (TKIs): analyses based on PACE and Optic. Blood. 2020;136(suppl 1):43-44. - PubMed
  61. Saussele S, Richter J, Guilhot J, et al. Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial. Lancet Oncol. 2018;19:747-757. - PubMed
  62. Hochhaus A, Masszi T, Giles FJ, et al. Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENESTfreedom study. Leukemia. 2017;31:1525-1531. - PubMed
  63. Chamoun K, Kantarjian H, Atallah R, et al. Tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia: a single-institution experience. J Hematol Oncol. 2019;12:1. - PubMed
  64. Hughes TP, Mauro MJ, Cortes JE, et al. Asciminib in chronic myeloid leukemia after ABL kinase inhibitor failure. N Engl J Med. 2019;381:2315-2326. - PubMed
  65. Jiang Q, Hunag X, Chen Z, et al. An updated safety and efficacy results of phase 1 study of HQP1351, a novel 3rd generation of BCR-ABL tyrosine kinase inhibitor (TKI), in patients with TKI resistant chronic myeloid leukemia. Blood. 2019;134:493. - PubMed
  66. Cortes J, Saikia T, Kim DW, et al. Phase 1 trial of vodobatinib, a novel oral BCR-ABL1 tyrosine kinase inhibitor (TKI): activity in CML chronic phase patients failing TKI therapies including ponatinib. Blood. 2020;136(suppl 1):51-52. - PubMed
  67. Jain N, Bueso-Ramos C, O'Brien S, Wierda WG. Chronic lymphocytic leukemia and associated disorders. In: Kantarjian HM, Wolff RA, eds. The MD Anderson Manual of Medical Oncology. McGraw-Hill; 2016:41-60. - PubMed
  68. Burger JA. Treatment of chronic lymphocytic leukemia. N Engl J Med. 2020;383:460-473. - PubMed
  69. Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008;111:5446-5456. - PubMed
  70. French Cooperative Group on Chronic Lymphocytic Leukemia. Effects of chlorambucil and therapeutic decision in initial forms of chronic lymphocytic leukemia (stage A): results of a randomized clinical trial on 612 patients. Blood. 1990;75:1414-1421. - PubMed
  71. Thompson PA, Tam CS, O'Brien SM, et al. Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia. Blood. 2016;127:303-309. - PubMed
  72. Fischer K, Bahlo J, Fink AM, et al. Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood. 2016;127:208-215. - PubMed
  73. Chai-Adisaksopha C, Brown JR. FCR achieves long-term durable remissions in patients with IGHV-mutated CLL. Blood. 2017;130:2278-2282. - PubMed
  74. Keating MJ, Kantarjian H, Talpaz M, et al. Fludarabine: a new agent with major activity against chronic lymphocytic leukemia. Blood. 1989;74:19-25. - PubMed
  75. Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010;376:1164-1174. - PubMed
  76. Eichhorst B, Fink AM, Busch R, et al. Frontline chemoimmunotherapy with fludarabine (F), cyclophosphamide (C), and rituximab (R) (FCR) shows superior efficacy in comparison to bendamustine (B) and rituximab (BR) in previously untreated and physically fit patients (pts) with advanced chronic lymphocytic leukemia (CLL): final analysis of an international, randomized study of the German CLL Study Group (GCLLSG). Blood. 2014;124:19. doi:10.1182/blood.V124.21.19.19 - PubMed
  77. Burger JA, Barr PM, Robak T, et al. Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study. Leukemia. 2020;34:787-798. - PubMed
  78. Byrd JC, Furman RR, Coutre SE, et al. Ibrutinib treatment for first-line and relapsed/refractory chronic lymphocytic leukemia: final analysis of the pivotal phase Ib/II PCYC-1102 study. Clin Cancer Res. 2020;26:3918-3927. - PubMed
  79. Byrd JC, Harrington B, O'Brien S, et al. Acalabrutinib (ACP-196) in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016;374:323-332. - PubMed
  80. Roberts AW, Davids MS, Pagel JM, et al. Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016;374:311-322. - PubMed
  81. Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax-rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378:1107-1120. - PubMed
  82. Davids MS, Kim HT, Brander DM, et al. A multicenter, phase II study of ibrutinib plus FCR (iFCR) as frontline therapy for younger CLL patients. Blood. 2017;130:496. - PubMed
  83. Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Lancet. 2020;395:1278-1291. - PubMed
  84. Tam CS, Robak T, Ghia P, et al. Zanubrutinib monotherapy for patients with treatment naive chronic lymphocytic leukemia and 17p deletion. Haematologica. 2020;106:2354-2363. - PubMed
  85. Mato AR, Shah NN, Jurczak W, et al. Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study. Lancet. 2021;397:892-901. - PubMed
  86. Wierda WG, Tam CS, Allan JN, et al. Ibrutinib (Ibr) plus venetoclax (Ven) for first-line treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): 1-year disease-free survival (DFS) results from the MRD cohort of the phase 2 CAPTIVATE study. Blood. 2020;136(suppl 1):16-17. - PubMed
  87. Hillmen P, Rawstron AC, Brock K, et al. Ibrutinib plus venetoclax in relapsed/refractory chronic lymphocytic leukemia: the CLARITY study. J Clin Oncol. 2019;37:2722-2729. - PubMed
  88. Soumerai JD, Mato AR, Carter J, et al. Initial results of a multicenter, investigator initiated study of MRD driven time limited therapy with zanubrutinib, obinutuzumab, and venetoclax. J Clin Oncol. 2020;38:8006. - PubMed
  89. Pui CH, Evans WE. A 50-year journey to cure childhood acute lymphoblastic leukemia. Semin Hematol. 2013;50:185-196. - PubMed
  90. Jabbour E, O'Brien S, Konopleva M, Kantarjian H. New insights into the pathophysiology and therapy of adult acute lymphoblastic leukemia. Cancer. 2015;121:2517-2528. - PubMed
  91. Jabbour E, Pui CH, Kantarjian H. Progress and innovations in the management of adult acute lymphoblastic leukemia. JAMA Oncol. 2018;4:1413-1420. - PubMed
  92. Jabbour E, O'Brien S, Ravandi F, Kantarjian H. Monoclonal antibodies in acute lymphoblastic leukemia. Blood. 2015;125:4010-4016. - PubMed
  93. Stock W, Luger SM, Advani AS, et al. A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: results of CALGB 10403. Blood. 2019;133:1548-1559. - PubMed
  94. Huguet F, Leguay T, Raffoux E, et al. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009;27:911-918. - PubMed
  95. Rytting ME, Jabbour EJ, Jorgensen JL, et al. Final results of a single institution experience with a pediatric-based regimen, the augmented Berlin-Frankfurt-Munster, in adolescents and young adults with acute lymphoblastic leukemia, and comparison to the hyper-CVAD regimen. Am J Hematol. 2016;91:819-823. - PubMed
  96. Rytting ME, Jabbour EJ, O'Brien SM, Kantarjian HM. Acute lymphoblastic leukemia in adolescents and young adults. Cancer. 2017;123:2398-2403. - PubMed
  97. Jabbour E, Richard-Carpentier G, Sasaki Y, et al. Hyper-CVAD regimen in combination with ofatumumab as frontline therapy for adults with Philadelphia chromosome-negative B-cell acute lymphoblastic leukaemia: a single-arm, phase 2 trial. Lancet Haematol. 2020;7:e523-e533. - PubMed
  98. Liu YF, Wang BY, Zhang WN, et al. Genomic profiling of adult and pediatric B-cell acute lymphoblastic leukemia. EBioMedicine. 2016;8:173-183. - PubMed
  99. Roberts KG, Pei D, Campana D, et al. Outcomes of children with BCR-ABL1-like acute lymphoblastic leukemia treated with risk-directed therapy based on the levels of minimal residual disease. J Clin Oncol. 2014;32:3012-3020. - PubMed
  100. Tasian SK, Loh ML, Hunger SP. Philadelphia chromosome-like acute lymphoblastic leukemia. Blood. 2017;130:2064-2072. - PubMed
  101. Jain N, Roberts KG, Jabbour E, et al. Ph-like acute lymphoblastic leukemia: a high-risk subtype in adults. Blood. 2017;129:572-581. - PubMed
  102. Roberts KG, Gu Z, Payne-Turner D, et al. High frequency and poor outcome of Philadelphia chromosome-like acute lymphoblastic leukemia in adults. J Clin Oncol. 2017;35:394-401. - PubMed
  103. Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378:439-448. - PubMed
  104. Park JH, Riviere I, Gonen M, et al. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med. 2018;378:449-459. - PubMed
  105. Kantarjian HM, DeAngelo DJ, Stelljes M, et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med. 2016;375:740-753. - PubMed
  106. Kantarjian H, Stein A, Gokbuget N, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376:836-847. - PubMed
  107. Brown PA, Ji L, Xu X, et al. Effect of postreinduction therapy consolidation with blinatumomab vs chemotherapy on disease-free survival in children, adolescents, and young adults with first relapse of B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. 2021;325:833-842. - PubMed
  108. Locatelli F, Zugmaier G, Rizzari C, et al. Effect of blinatumomab vs chemotherapy on event-free survival among children with high-risk first-relapse B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. 2021;325:843-854. - PubMed
  109. Rausch CR, Jabbour EJ, Kantarjian HM, Kadia TM. Optimizing the use of the hyperCVAD regimen: clinical vignettes and practical management. Cancer. 2020;126:1152-1160. - PubMed
  110. Daver N, Thomas D, Ravandi F, 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;100:653-661. - PubMed
  111. Ravandi F, O'Brien SM, Cortes JE, 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;121:4158-4164. - PubMed
  112. Ravandi F, Othus M, O'Brien SM, et al. US intergroup study of chemotherapy plus dasatinib and allogeneic stem cell transplant in Philadelphia chromosome positive ALL. Blood Adv. 2016;1:250-259. - PubMed
  113. Rousselot P, Coude MM, Gokbuget N, et al. Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome-positive ALL. Blood. 2016;128:774-782. - PubMed
  114. Jabbour E, Kantarjian H, Ravandi F, 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;16:1547-1555. - PubMed
  115. Short NJ, Kantarjian H, Konopleva MY, et al. Combination of ponatinib and blinatumomab in Philadelphia chromosome-positive acute lymphoblastic leukemia: early results from a phase II study. J Clin Oncol. 2021;39(suppl):7001. - PubMed
  116. Thomas DA, Faderl S, O'Brien S, et al. Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Cancer. 2006;106:1569-1580. - PubMed
  117. Thomas DA, O'Brien S, Faderl S, et al. Chemoimmunotherapy with a modified hyper-CVAD and rituximab regimen improves outcome in de novo Philadelphia chromosome-negative precursor B-lineage acute lymphoblastic leukemia. J Clin Oncol. 2010;28:3880-3889. - PubMed
  118. Ribrag V, Koscielny S, Bosq J, et al. Rituximab and dose-dense chemotherapy for adults with Burkitt's lymphoma: a randomised, controlled, open-label, phase 3 trial. Lancet. 2016;387:2402-2411. - PubMed
  119. Maury S, Chevret S, Thomas X, et al. Rituximab in B-lineage adult acute lymphoblastic leukemia. N Engl J Med. 2016;375:1044-1053. - PubMed
  120. Topp MS, Gokbuget 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;16:57-66. - PubMed
  121. Kantarjian H, Ravandi F, Short NJ, et al. Inotuzumab ozogamicin in combination with low-intensity chemotherapy for older patients with Philadelphia chromosome-negative acute lymphoblastic leukaemia: a single-arm, phase 2 study. Lancet Oncol. 2018;19:240-248. - PubMed
  122. 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;119:2728-2736. - PubMed
  123. Short NJ, Jabbour E, Albitar M, et al. Recommendations for the assessment and management of measurable residual disease in adults with acute lymphoblastic leukemia: a consensus of North American experts. Am J Hematol. 2019;94:257-265. - PubMed
  124. Gökbuget N, Dombret H, Bonifacio M, et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018;131:1522-1531. - PubMed
  125. Sasaki K, Kantarjian H, Morita K, et al. Hyper-CVAD plus ofatumumab versus hyper-CVAD with or without rituximab as frontline therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: a propensity score analysis. Cancer. 2021;127:3381-3389. - PubMed
  126. Short NJ, Kantarjian H, Ravandi F, et al. Hyper-CVAD and sequential blinatumomab in adults with newly diagnosed Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia: results from a phase II study. Blood. 2020;136(suppl 1):9-11. - PubMed
  127. Olszewski A, Avigdor A, Babu S, et al. Single-agent mosunetuzumab is a promising safe and efficacious chemotherapy-free regimen for elderly/unfit patients with previously untreated diffuse large B-cell lymphoma. Blood. 2020;136(suppl 1):43-45. - PubMed
  128. Bannerji R, Allan JN, Arnason JE, et al. Odronextamab (REGN1979), a human CD20 × CD3 bispecific antibody, induces durable, complete responses in patients with highly refractory B-cell non-Hodgkin lymphoma, including patients refractory to CAR T therapy. Blood. 2020;136(suppl 1):42-43. - PubMed
  129. Garfall AL, June CH. Trispecific antibodies offer a third way forward for anticancer immunotherapy. Nature. 2019;575:450-451. - PubMed
  130. Qin H, Ramakrishna S, Nguyen S, et al. Preclinical development of bivalent chimeric antigen receptors targeting both CD19 and CD22. Mol Ther Oncolytics. 2018;11:127-137. - PubMed
  131. Hu P, Xiong Y, Wu D, et al. Fully human tandem CD22-CD19 CAR-T cells with superior sensitivity to low antigen density derived by optimization of co-stimulation and CAR architecture. Blood. 2020;136(suppl 1):12-13. - PubMed
  132. Shen S, Chen X, Cai J, et al. Effect of dasatinib vs imatinib in the treatment of pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia: a randomized clinical trial. JAMA Oncol. 2020;6:358-366. - PubMed
  133. Ribera JM, Garcia O, Montesinos P, et al. Ponatinib and chemotherapy in young adults with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia. Results of ponalfil clinical trial after completion of recruitment. Blood. 2020;136(suppl 1):29-30. - PubMed
  134. Jabbour E, DerSarkissian M, Duh MS, et al. Efficacy of ponatinib versus earlier generation tyrosine kinase inhibitors for front-line treatment of newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Clin Lymphoma Myeloma Leuk. 2018;18:257-265. - PubMed
  135. Sasaki K, Jabbour EJ, Ravandi F, 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;122:3650-3656. - PubMed
  136. Martinelli G, Piciocchi A, Papayannidis C, 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;130(suppl 1):99. - PubMed
  137. Martinelli G, Boissel N, Chevallier P, et al. Complete hematologic and molecular response in adult patients with relapsed/refractory Philadelphia chromosome-positive B-precursor acute lymphoblastic leukemia following treatment with blinatumomab: results from a phase II, single-arm, multicenter study. J Clin Oncol. 2017;35:1795-1802. - PubMed
  138. Rambaldi A, Ribera JM, Kantarjian HM, et al. Blinatumomab compared with standard of care for the treatment of adult patients with relapsed/refractory Philadelphia chromosome-positive B-precursor acute lymphoblastic leukemia. Cancer. 2020;126:304-310. - PubMed
  139. Stock W, Martinelli G, Stelljes M, et al. Efficacy of inotuzumab ozogamicin in patients with Philadelphia chromosome-positive relapsed/refractory acute lymphoblastic leukemia. Cancer. 2021;127:905-913. - PubMed
  140. Assi R, Kantarjian H, Short NJ, 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;17:897-901. - PubMed
  141. Jabbour E, Kantarjian H. A new era in the treatment of acute lymphoblastic leukemia. Blood. 2021;137:1563-1564. - PubMed
  142. Kantarjian H, Thomas D, Wayne AS, O'Brien S. Monoclonal antibody-based therapies: a new dawn in the treatment of acute lymphoblastic leukemia. J Clin Oncol. 2012;30:3876-3883. - PubMed
  143. Jabbour E, Ravandi F, Kebriaei P, et al. 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. 2018;4:230-234. - PubMed
  144. Jabbour E, Sasaki K, Short NJ, et al. Long-term follow-up of salvage therapy using a combination of inotuzumab ozogamicin and mini-hyper-CVD with or without blinatumomab in relapsed/refractory Philadelphia chromosome-negative acute lymphoblastic leukemia. Cancer. 2021;127:2025-2038. - PubMed
  145. Jabbour EJ, Sasaki K, Ravandi F, et al. Inotuzumab ozogamicin in combination with low-intensity chemotherapy (mini-HCVD) with or without blinatumomab versus standard intensive chemotherapy (HCVAD) as frontline therapy for older patients with Philadelphia chromosome-negative acute lymphoblastic leukemia: a propensity score analysis. Cancer. 2019;125:2579-2586. - PubMed
  146. Stelljes M, Raffel S, Wäsch R, et al. First results of an open label phase II study to evaluate the efficacy and safety of inotuzumab ozogamicin for induction therapy followed by a conventional chemotherapy based consolidation and maintenance therapy in patients aged 56 years and older with acute lymphoblastic leukemia (INITIAL-1 trial). Blood. 2020;136(suppl 1):12-13. - PubMed
  147. Kadia TM, Ravandi F, Cortes J, Kantarjian H. Toward individualized therapy in acute myeloid leukemia: a contemporary review. JAMA Oncol. 2015;1:820-828. - PubMed
  148. Kantarjian H. Acute myeloid leukemia-major progress over four decades and glimpses into the future. Am J Hematol. 2016;91:131-145. - PubMed
  149. Kantarjian H, Short NJ, Fathi AT, et al. Acute myeloid leukemia-historical perspective and progress in research and therapy over five decades. Clin Lymphoma Myeloma Leuk. 2021;21:580-597. - PubMed
  150. Sasaki K, Ravandi F, Kadia TM, et al. De novo acute myeloid leukemia: a population-based study of outcome in the United States based on the Surveillance, Epidemiology, and End Results (SEER) database, 1980 to 2017. Cancer. Published online April 5, 2021. doi:10.1002/cncr.33458 - PubMed
  151. Bhatt VR, Shostrom V, Giri S, et al. Early mortality and overall survival of acute myeloid leukemia based on facility type. Am J Hematol. 2017;92:764-771. - PubMed
  152. Ho G, Wun T, Muffly L, et al. Decreased early mortality associated with the treatment of acute myeloid leukemia at National Cancer Institute-designated cancer centers in California. Cancer. 2018;124:1938-1945. - PubMed
  153. Kantarjian H, Short NJ, DiNardo C, et al. Harnessing the value of available targeted therapies in adult myeloid leukemia. Lancet Haematol. Forthcoming 2021. - PubMed
  154. DiNardo C, Lachowiez C, Takahashi K, et al. Venetoclax combined with FLAG-IDA induction and consolidation in newly diagnosed and relapsed or refractory acute myeloid leukemia. J Clin Oncol. 2021;39:2768-2778. - PubMed
  155. Kadia TM, Reville PK, Borthakur G, et al. Venetoclax plus intensive chemotherapy with cladribine, idarubicin, and cytarabine in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a cohort from a single-centre, single-arm, phase 2 trial. Lancet Haematol. 2021;8:e552-e561. doi:10.1016/S2352-3026(21)00192-7 - PubMed
  156. Stone RM, Mandrekar SJ, Sanford BL, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017;377:454-464. - PubMed
  157. Pratz K, Cherry M, Altman J, et al. A phase 1 study of gilteritinib in combination with induction and consolidation chemotherapy in patients with newly diagnosed AML: final results. Blood. 2020;136(suppl 1):16-17. - PubMed
  158. Rollig C, Serve H, Noppeney R, et al. Sorafenib or placebo in patients with newly diagnosed acute myeloid leukaemia: long-term follow-up of the randomized controlled SORAML trial. Leukemia. 2021;35:2517-2525. - PubMed
  159. Stein E, DiNardo CD, Fathi AT, et al. Ivosidenib or enasidenib combined with intensive chemotherapy in patients with newly diagnosed AML: a phase 1 study. Blood. 2021;137:1792-1803. - PubMed
  160. Chua CC, Roberts AW, Reynolds J, et al. Chemotherapy and Venetoclax in Elderly Acute Myeloid Leukemia Trial (CAVEAT): a phase Ib dose-escalation study of venetoclax combined with modified intensive chemotherapy. J Clin Oncol. 2020;38:3506-3517. - PubMed
  161. Plimack ER, Kantarjian HM, Issa JP. Decitabine and its role in the treatment of hematopoietic malignancies. Leuk Lymphoma. 2007;48:1472-1481. - PubMed
  162. Jabbour E, Issa JP, Garcia-Manero G, Kantarjian H. Evolution of decitabine development: accomplishments, ongoing investigations, and future strategies. Cancer. 2008;112:2341-2351. - PubMed
  163. Kantarjian HM, O'Brien S, Huang X, et al. Survival advantage with decitabine versus intensive chemotherapy in patients with higher risk myelodysplastic syndrome: comparison with historical experience. Cancer. 2007;109:1133-1137. - PubMed
  164. Kantarjian HM, O'Brien S, Shan J, et al. Update of the decitabine experience in higher risk myelodysplastic syndrome and analysis of prognostic factors associated with outcome. Cancer. 2007;109:265-273. - PubMed
  165. Burnett AK, Milligan D, Prentice AG, et al. A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment. Cancer. 2007;109:1114-1124. - PubMed
  166. Kantarjian HM, Thomas XG, Dmoszynska A, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012;30:2670-2677. - PubMed
  167. Dombret H, Seymour JF, Butrym A, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015;126:291-299. - PubMed
  168. Kadia TM, Faderl S, Ravandi F, et al. Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia. Cancer. 2015;121:2375-2382. - PubMed
  169. Kadia TM, Cortes J, Ravandi F, et al. Cladribine and low-dose cytarabine alternating with decitabine as front-line therapy for elderly patients with acute myeloid leukaemia: a phase 2 single-arm trial. Lancet Haematol. 2018;5:e411-e421. - PubMed
  170. Kadia TM, Ravandi F, Borthakur G, et al. Long-term results of low-intensity chemotherapy with clofarabine or cladribine combined with low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia. Am J Hematol. Published online April 26, 2021. doi:10.1002/ajh.26206 - PubMed
  171. DiNardo CD, Pratz KW, Letai A, et al. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018;19:216-228. - PubMed
  172. Wei AH, Strickland SA Jr, Hou JZ, et al. Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia: results from a phase Ib/II study. J Clin Oncol. 2019;37:1277-1284. - PubMed
  173. Wei AH, Montesinos P, Ivanov V, et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood. 2020;135:2137-2145. - PubMed
  174. DiNardo C, Maiti A, Rausch C, et al. 10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial. Lancet Haematol. 2020;10:e724-e736. - PubMed
  175. Kadia T, Cortes J, Konopleva M, et al. Venetoclax combined with cladribine + low dose AraC (LDAC) alternating with 5-azacytidine produces high rates of minimal residual disease (MRD) negative complete remissions (CR) in older patients with newly diagnosed acute myeloid leukemia (AML). Blood. 2020;136(suppl 1):25. - PubMed
  176. Xuan L, Wang Y, Huang F, et al. Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised phase 3 trial. Lancet Oncol. 2020;21:1201-1212. - PubMed
  177. Burchert A, Bug G, Fritz LV, et al. Sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with FLT3-internal tandem duplication mutation (SORMAIN). J Clin Oncol. 2020;38:2993-3002. - PubMed
  178. Garcia-Manero G, Griffiths EA, Steensma DP, et al. Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Blood. 2020;136:674-683. - PubMed
  179. Savona M, McCloskey J, Griffiths E, et al. Clinical efficacy and safety of oral decitabine/cedaduridine in 133 patients with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). Blood. 2020;126:1230. - PubMed
  180. Wang E, Altman J, Pettit K, et al. Preliminary data on a phase 1/2A first in human study of the menin-KMT2A (MLL) inhibitor KO-539 in patients with relapsed or refractory acute myeloid leukemia. Blood. 2020;136(suppl 1):7-8. - PubMed
  181. CICR spring 2020 newsletter: selected research highlights. American Association for Cancer Research. Accessed March 9, 2021. https://www.aacr.org/wp-content/uploads/2020/06/CICR_Newsletter_June_2020.pdf - PubMed
  182. DiNardo C, Garcia-Manero G, Pierce S, et al. Interactions and relevance of blast percentage and treatment strategies among younger and older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Am J Hematol. 2016;91:227-232. - PubMed

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