Efficacy and biological correlates of response in a phase II study of venetoclax monotherapy in patients with acute Myelogenous Leukemia

Cancer Discovery

Volumn 6, Issue 10, 2016, Pages 1106-1117

  Konopleva, Marina ^a   Pollyea, Daniel A ^b   Potluri, Jalaja ^c   Chyla, Brenda ^c   Hogdal, Leah ^d   Busman, Todd ^c   McKeegan, Evelyn ^c   Salem, Ahmed Hamed ^c,e   Zhu, Ming ^c   Ricker, Justin L ^c   Blum, William ^f   Dinardo, Courtney D ^a   Kadia, Tapan ^a   Dunbar, Martin ^c   Kirby, Rachel ^c   Falotico, Nancy ^c   Leverson, Joel ^c   Humerickhouse, Rod ^c   Mabry, Mack ^c   Stone, Richard ^d   Kantarjian, Hagop ^a   Letai, Anthony ^d   more..

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b UNIVERSITY OF COLORADO CANCER CENTER   (United States)

^c ABBVIE INC   (United States)

^d DANA FARBER CANCER INSTITUTE   (United States)

^e Ain Shams University   (Egypt)

^f OHIO STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ISOCITRATE DEHYDROGENASE; PROTEIN BCL 2; VENETOCLAX; ANTINEOPLASTIC AGENT; FUSED HETEROCYCLIC RINGS; SULFONAMIDE;

ACUTE MYELOBLASTIC LEUKEMIA; ADULT; AGED; ARTICLE; CLINICAL ARTICLE; CLINICAL ASSESSMENT; DIARRHEA; DRUG EFFICACY; DRUG TOLERABILITY; FEBRILE NEUTROPENIA; FEMALE; GENE MUTATION; HUMAN; HYPOKALEMIA; MALE; NAUSEA AND VOMITING; PHASE 2 CLINICAL TRIAL; TREATMENT RESPONSE; VERY ELDERLY; CLINICAL TRIAL; DISEASE FREE SURVIVAL; DRUG ADMINISTRATION; LEUKEMIA, MYELOID, ACUTE; MIDDLE AGED; ORAL DRUG ADMINISTRATION; SURVIVAL ANALYSIS; TREATMENT OUTCOME; YOUNG ADULT;

ADMINISTRATION, ORAL; ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC AGENTS; BRIDGED BICYCLO COMPOUNDS, HETEROCYCLIC; DISEASE-FREE SURVIVAL; DRUG ADMINISTRATION SCHEDULE; FEMALE; HUMANS; LEUKEMIA, MYELOID, ACUTE; MALE; MIDDLE AGED; SULFONAMIDES; SURVIVAL ANALYSIS; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84994106763     PISSN: 21598274     EISSN: 21598290     Source Type: Journal    
DOI: 10.1158/2159-8290.CD-16-0313     Document Type: Article

References (40)

1. Kantarjian H, O’Brien S, Cortes J, Giles F, Faderl S, Jabbour E, et al. Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: Predictive prognostic models for outcome. Cancer 2006; 106: 1090–8.
2. Kantarjian H, Ravandi F, O’Brien S, Cortes J, Faderl S, Garcia- Manero G, et al. Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia. Blood 2010; 116: 4422–9.
3. Adams JM, Cory S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 2007; 26: 1324–37.
4. Certo M, Del Gaizo Moore V, Nishino M, Wei G, Korsmeyer S, Armstrong SA, et al. Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. Cancer Cell 2006; 9: 351–65.
5. Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med 2013; 19: 202–8.
6. Vogler M, Dinsdale D, Dyer MJ, Cohen GM. ABT-199 selectively inhibits BCL2 but not BCL2L1 and efficiently induces apoptosis of chronic lymphocytic leukaemic cells but not platelets. Br J Haematol 2013; 163: 139–42.
7. Pan R, Hogdal LJ, Benito JM, Bucci D, Han L, Borthakur G, et al. Selective BCL-2 inhibition by ABT-199 causes on-target cell death in acute myeloid leukemia. Cancer Discov 2014; 4: 362–75.
8. Leverson JD, Phillips DC, Mitten MJ, Boghaert ER, Diaz D, Tahir SK, et al. Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy. Sci Transl Med 2015; 7: 279ra40.
9. Konopleva M, Contractor R, Tsao T, Samudio I, Ruvolo PP, Kitada S, et al. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell 2006; 10: 375–88.
10. Lagadinou ED, Sach A, Callahan K, Rossi RM, Neering SJ, Minhajuddin M, et al. BCL-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent human leukemia stem cells. Cell Stem Cell 2013; 12: 329–41.
11. Vo TT, Ryan J, Carrasco R, Neuberg D, Rossi DJ, Stone RM, et al. Relative mitochondrial priming of myeloblasts and normal HSCs determines chemotherapeutic success in AML. Cell 2012; 151: 344–55.
12. 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: 311–22.
13. Gross S, Cairns RA, Minden MD, Driggers EM, Bittinger MA, Jang HG, et al. Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations. J Exp Med 2010; 207: 339–44.
14. Mardis ER, Ding L, Dooling DJ, Larson DE, McLellan MD, Chen K, et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med 2009; 361: 1058–66.
15. Patel JP, Gonen M, Figueroa ME, Fernandez H, Sun Z, Racevskis J, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med 2012; 366: 1079–89.
16. Del Gaizo Moore V, Letai A. BH3 profiling–measuring integrated function of the mitochondrial apoptotic pathway to predict cell fate decisions. Cancer Lett 2013; 332: 202–5.
17. Chonghaile TN, Roderick JE, Glenfield C, Ryan J, Sallan SE, Silverman LB, et al. Maturation stage of T-cell acute lymphoblastic leukemia determines BCL-2 versus BCL-XL dependence and sensitivity to ABT-199. Cancer Discov 2014; 4: 1074–87.
18. Davids MS, Seymour JF, Gerecitano JF, Kahl BS, Pagel JM, Wierda WG, et al. Phase I study of ABT-199 (GDC-0199) in patients with relapsed/refractory non-Hodgkin lymphoma: responses observed in diffuse large B-cell (DLBCL) and follicular lymphoma (FL) at higher cohort doses. J Clin Oncol 32: 5s, 2014 (suppl: abstr 8522).
19. Appelbaum FR, Gundacker H, Head DR, Slovak ML, Willman CL, Godwin JE, et al. Age and acute myeloid leukemia. Blood 2006; 107: 3481–5.
20. Pinto A, Zagonel V, Ferrara F. Acute myeloid leukemia in the elderly: Biology and therapeutic strategies. Crit Rev Oncol Hematol 2001; 39: 275–87.
21. DiNardo CD, Ravandi F, Agresta S, Konopleva M, Takahashi K, Kadia T, et al. Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML. Am J Hematol 2015; 90: 732–6.
22. Chan SM, Majeti R. Role of DNMT3A, TET2, and IDH1/2 mutations in pre-leukemic stem cells in acute myeloid leukemia. Int J Hematol 2013; 98: 648–57.
23. Corces-Zimmerman MR, Hong WJ, Weissman IL, Medeiros BC, Majeti R. Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission. Proc Natl Acad Sci U S A 2014; 111: 2548–53.
24. Chou WC, Hou HA, Chen CY, Tang JL, Yao M, Tsay W, et al. Distinct clinical and biologic characteristics in adult acute myeloid leukemia bearing the isocitrate dehydrogenase 1 mutation. Blood 2010; 115: 2749–54.
25. Chou WC, Lei WC, Ko BS, Hou HA, Chen CY, Tang JL, et al. The prognostic impact and stability of isocitrate dehydrogenase 2 mutation in adult patients with acute myeloid leukemia. Leukemia 2011; 25: 246–53.
26. Chan SM, Thomas D, Corces-Zimmerman MR, Xavy S, Rastogi S, Hong WJ, et al. Isocitrate dehydrogenase 1 and 2 mutations induce BCL-2 dependence in acute myeloid leukemia. Nat Med 2015; 21: 178–84.
27. Roberts AW, Seymour JF, Brown JR, Wierda WG, Kipps TJ, Khaw SL, et al. Substantial susceptibility of chronic lymphocytic leukemia to BCL2 inhibition: results of a phase I study of navitoclax in patients with relapsed or refractory disease. J Clin Oncol 2012; 30: 488–96.
28. Kipps TJ, Eradat H, Grosicki S, Catalano J, Cosolo W, Dyagil IS, et al. A phase 2 study of the BH3 mimetic BCL2 inhibitor navitoclax (ABT-263) with or without rituximab, in previously untreated B-cell chronic lymphocytic leukemia. Leuk Lymphoma 2015; 56: 2826–33.
29. Rudin CM, Hann CL, Garon EB, Ribeiro de Oliveira M, Bonomi PD, Camidge DR, et al. Phase II study of single-agent navitoclax (ABT- 263) and biomarker correlates in patients with relapsed small cell lung cancer. Clin Cancer Res 2012; 18: 3163–9.
30. Merino D, Khaw SL, Glaser SP, Anderson DJ, Belmont LD, Wong C, et al. Bcl-2, Bcl-x(L), and Bcl-w are not equivalent targets of ABT-737 and navitoclax (ABT-263) in lymphoid and leukemic cells. Blood 2012; 119: 5807–16.
31. Ishizawa J, Kojima K, McQueen T, Ruvolo V, Chachad D, Nogueras- Gonzalez GM, et al. Mitochondrial profiling of acute myeloid Leukemia in the assessment of response to apoptosis modulating drugs. PLoS One 2015; 10: e0138377.
32. Pierceall WE, Kornblau SM, Carlson NE, Huang X, Blake N, Lena R, et al. BH3 profiling discriminates response to cytarabine-based treatment of acute myelogenous leukemia. Mol Cancer Ther 2013; 12: 2940–9.
33. Del Gaizo Moore V, Brown JR, Certo M, Love TM, Novina CD, Letai A. Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737. J Clin Invest 2007; 117: 112–21.
34. Breems DA, Van Putten WL, Huijgens PC, Ossenkoppele GJ, Verhoef GE, Verdonck LF, et al. Prognostic index for adult patients with acute myeloid leukemia in first relapse. J Clin Oncol 2005; 23: 1969–78.
35. Chevallier P, Labopin M, Turlure P, Prebet T, Pigneux A, Hunault M, et al. A new Leukemia Prognostic Scoring System for refractory/ relapsed adult acute myelogeneous leukaemia patients: A GOELAMS Study. Leukemia 2011; 25: 939–44
36. Thol F, Schlenk RF, Heuser M, Ganser A. How I treat refractory and early relapsed acute myeloid leukemia. Blood 2015; 126: 319–27.
37. Bogenberger JM, Delman D, Hansen N, Valdez R, Fauble V, Mesa RA, et al. Ex vivo activity of BCL-2 family inhibitors ABT-199 and ABT-737 combined with 5-azacytidine in myeloid malignancies. Leuk Lymphoma 2015; 56: 226–9.
38. Tsao T, Shi Y, Kornblau S, Lu H, Konoplev S, Antony A, et al. Concomitant inhibition of DNA methyltransferase and BCL-2 protein function synergistically induce mitochondrial apoptosis in acute myelogenous leukemia cells. Ann Hematol 2012; 91: 1861–70.
39. DiNardo C, Pollyea D, Pratz K, Thirman MJ, Letai A, Frattini M, et al. A phase 1b study of venetoclax (ABT-199/GDC-0199) in combination with decitabine or azacitidine in treatment-naive patients with acute myelogenous leukemia who are ≥ to 65 years and not eligible for standard induction therapy. Blood 2015; 126: 327.
40. Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 2003; 21: 4642–9.