Long-term results of the phase II trial of the oral mTOR inhibitor everolimus (RAD001) in relapsed or refractory Waldenstrom Macroglobulinemia

American Journal of Hematology

Volumn 89, Issue 3, 2014, Pages 237-242

  Ghobrial, Irene M ^a   Witzig, Thomas E ^b   Gertz, Morie ^b   Laplant, Betsy ^b   Hayman, Suzanne ^b   Camoriano, John ^b   Lacy, Martha ^b   Bergsagel, P Leif ^c   Chuma, Stacey ^a   Deangelo, Daniel ^a   Treon, Steven P ^a  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b Mayo Clinic College of Medicine   (United States)

^c MAYO CLINIC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA 2 MICROGLOBULIN; EVEROLIMUS; HEMOGLOBIN; IMMUNOGLOBULIN M; STEROID;

ADULT; AGED; ANEMIA; ARTHRALGIA; ARTICLE; BLOOD TOXICITY; BONE MARROW SUPPRESSION; BRAIN HEMATOMA; CANCER SURVIVAL; CAUSE OF DEATH; CELLULITIS; CONGESTIVE HEART FAILURE; DIARRHEA; DISEASE COURSE; DRUG DOSE REDUCTION; DRUG WITHDRAWAL; DYSPNEA; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; FOLLOW UP; HEADACHE; HUMAN; HYPERCHOLESTEROLEMIA; HYPERGLYCEMIA; HYPERTRIGLYCERIDEMIA; HYPOGLYCEMIA; HYPONATREMIA; IMMUNOGLOBULIN BLOOD LEVEL; LEUKOPENIA; LUNG TOXICITY; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; MOUTH ULCER; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; NEUTROPHIL COUNT; OUTCOME ASSESSMENT; OVERALL SURVIVAL; PERIPHERAL EDEMA; PHASE 2 CLINICAL TRIAL (TOPIC); PLEURA EFFUSION; PNEUMONIA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RECURRENT DISEASE; SEPSIS; SQUAMOUS CELL CARCINOMA; STOMATITIS; THROMBOCYTE COUNT; THROMBOCYTOPENIA; TIME TO PROGRESSION; TREATMENT RESPONSE; UPPER RESPIRATORY TRACT INFECTION; VERY ELDERLY; WALDENSTROEM MACROGLOBULINEMIA;

ADULT; AGED; AGED, 80 AND OVER; ALKYLATING AGENTS; ANGIOGENESIS INHIBITORS; ANTIBODIES, MONOCLONAL, MURINE-DERIVED; ANTIMETABOLITES; BONE MARROW; DIARRHEA; DISEASE-FREE SURVIVAL; DRUG RESISTANCE; FATIGUE; FEMALE; HEMATOLOGIC DISEASES; HUMANS; IMMUNOGLOBULIN M; KAPLAN-MEIER ESTIMATE; MALE; MIDDLE AGED; PAIN; PARAPROTEINS; RECURRENCE; SIROLIMUS; STOMATITIS; TOR SERINE-THREONINE KINASES; TREATMENT OUTCOME; WALDENSTROM MACROGLOBULINEMIA;

EID: 84896810498     PISSN: 03618609     EISSN: 10968652     Source Type: Journal    
DOI: 10.1002/ajh.23620     Document Type: Article

References (49)

1. Dimopoulos MA, Panayiotidis P, Moulopoulos LA, et al. Waldenstrom's macroglobulinemia: Clinical features, complications, and management. J Clin Oncol 2000;18:214-226.
2. Ghobrial IM, Witzig TE. Waldenstrom macroglobulinemia. Curr Treat Options Oncol 2004;5:239-247.
3. Dimopoulos MA, Kyle RA, Anagnostopoulos A, Treon SP. Diagnosis and management of Waldenstrom's macroglobulinemia. J Clin Oncol 2005;23:1564-1577.
4. Owen RG, Treon SP, Al-Katib A, et al. Clinicopathological definition of Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia. Semin Oncol 2003;30:110-115.
5. Treon SP, Xu L, Yang G, et al. MYD88 L265P somatic mutation in Waldenstrom's macroglobulinemia. N Engl J Med 2012;367:826-833.
6. Xu L, Hunter ZR, Yang G, et al. MYD88 L265P in Waldenstrom's macroglobulinemia, IgM monoclonal gammopathy, and other B-cell lymphoproliferative disorders using conventional and quantitative allele-specific PCR. Blood 2013;121:2051-2058.
7. Laird MH, Rhee SH, Perkins DJ, et al. TLR4/MyD88/PI3K interactions regulate TLR4 signaling. J Leukocyte Biol 2009;85:966-977.
8. Rhee SH, Kim H, Moyer MP, Pothoulakis C. Role of MyD88 in phosphatidylinositol 3-kinase activation by flagellin/toll-like receptor 5 engagement in colonic epithelial cells. J Biol Chem 2006;281:18560-18568.
9. Lee IT, Lee CW, Tung WH, et al. Cooperation of TLR2 with MyD88, PI3K, and Rac1 in lipoteichoic acid-induced cPLA2/COX-2-dependent airway inflammatory responses. Am J Pathol 2010;176:1671-1684.
10. Zhang Y, Roccaro AM, Rombaoa C, et al. LNA-mediated anti-miR-155 silencing in low-grade B-cell lymphomas. Blood 2012;120:1678-1686.
11. Roccaro AM, Sacco A, Chen C, et al. microRNA expression in the biology, prognosis, and therapy of Waldenstrom macroglobulinemia. Blood 2009;113:4391-4402.
12. Roccaro AM, Sacco A, Jia X, et al. Mechanisms of activity of the TORC1 inhibitor everolimus in Waldenstrom macroglobulinemia. Clin Cancer Res 2012;18:6609-6622.
13. Leblond V, Johnson S, Chevret S, et al. Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated Waldenstrom macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol 2013;31:301-307.
14. Anderson KC, Alsina M, Bensinger W, et al. Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma, version 2.2013. J Natl Comprehensive Cancer Netw 2012;10:1211-1219.
15. Pene F, Claessens YE, Muller O, et al. Role of the phosphatidylinositol 3-kinase/Akt and mTOR/P70S6-kinase pathways in the proliferation and apoptosis in multiple myeloma. Oncogene 2002;21:6587-6597.
16. Foster DA. Targeting mTOR-mediated survival signals in anticancer therapeutic strategies. Expert Rev Anticancer Ther 2004;4:691-701.
17. Shi Y, Sharma A, Wu H, et al. Cyclin D1 and c-Myc internal ribosome entry site (IRES)-dependent translation is regulated by AKT activity and enhanced by rapamycin through a p38 MAPK and ERK-dependent pathway. J Biol Chem 2005;280:10964-10973.
18. Choo AY, Blenis J. TORgeting oncogene addiction for cancer therapy. Cancer Cell 2006;9:77-79.
19. Thoreen CC, Kang SA, Chang JW, et al. An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J Biol Chem 2009;284:8023-8032.
20. Motzer RJ, Escudier B, Oudard S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008;372:449-456.
21. Treon SP. How I treat Waldenstrom macroglobulinemia. Blood 2009;114:2375-2385.
22. Chan S. Targeting the mammalian target of rapamycin (mTOR): A new approach to treating cancer. Br J Cancer. 2004;91:1420-1424.
23. Ghobrial I, Gertz M, LaPlant B, et al. Phase II Trial of the Oral Mammalian Target of Rapamycin Inhibitor Everolimus in Relapsed or Refractory Waldenström Macroglobulinemia. J Clin Oncol 2010;28:1408-1414.
24. Treon SP, Gertz MA, Dimopoulos M, et al. Update on treatment recommendations from the Third International Workshop on Waldenstrom's macroglobulinemia. Blood 2006;107:3442-3446.
25. Dimopoulos MA, Gertz MA, Kastritis E, et al. Update on treatment recommendations from the Fourth International Workshop on Waldenstrom's Macroglobulinemia. J Clin Oncol 2009;27:120-126.
26. Weber D, Treon SP, Emmanouilides C, et al. Uniform response criteria in Waldenstrom's macroglobulinemia: Consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia. Semin Oncol 2003;30:127-131.
27. Kaplan E, Meier P. Nonparametric estimation for incomplete observations. J Am Stat Assoc 1958;53:457-481.
28. Morel P, Duhamel A, Gobbi P, et al. International prognostic scoring system for Waldenstrom's macroglobulinemia. Blood 2009;113:4163-4170.
29. Kimby E, Treon SP, Anagnostopoulos A, et al. Update on recommendations for assessing response from the Third International Workshop on Waldenstrom's Macroglobulinemia. Clin Lymph Myeloma 2006;6:380-383.
30. Sacco A, Roccaro A, Ghobrial IM. Role of dual PI3/Akt and mTOR inhibition in Waldenstrom's Macroglobulinemia. Oncotarget 2010;1:578-582.
31. Ghobrial IM, Gertz M, Laplant B, et al. Phase II trial of the oral mammalian target of rapamycin inhibitor everolimus in relapsed or refractory Waldenstrom macroglobulinemia. J Clin Oncol 2010;28:1408-1414.
32. Dhodapkar MV, Jacobson JL, Gertz MA, et al. Prognostic factors and response to fludarabine therapy in Waldenstrom's macroglobulinemia: an update of a US intergroup trial (SW0G S9003). Semin Oncol 2003;30:220-225.
33. Gertz MA, Rue M, Blood E, et al. Multicenter phase 2 trial of rituximab for Waldenstrom macroglobulinemia (WM): An Eastern Cooperative Oncology Group Study (E3A98). Leuk Lymphoma 2004;45:2047-2055.
34. Dimopoulos MA, Zervas C, Zomas A, et al. Extended rituximab therapy for previously untreated patients with Waldenstrom's macroglobulinemia. Clin Lymphoma 2002;3:163-166.
35. Treon SP, Emmanouilides C, Kimby E, et al. Extended rituximab therapy in Waldenstrom's macroglobulinemia. Ann Oncol 2005;16:132-138.
36. Treon SP, Hunter ZR, Matous J, et al. Multicenter Clinical Trial of Bortezomib in Relapsed/Refractory Waldenstrom's Macroglobulinemia: Results of WMCTG Trial 03-248. Clin Cancer Res 2007;13:3320-3325.
37. Ghobrial IM, Roccaro A, Hong F, et al. Clinical and translational studies of a phase II trial of the novel oral Akt inhibitor perifosine in relapsed or relapsed/refractory Waldenstrom's macroglobulinemia. Clin Cancer Res 2010;16:1033-1041.
38. Ghobrial IM, Campigotto F, Murphy TJ, et al. Results of a phase 2 trial of the single-agent histone deacetylase inhibitor panobinostat in patients with relapsed/refractory Waldenstrom macroglobulinemia. Blood 2013;121:1296-1303.
39. Raje N, Kumar S, Hideshima T, et al. Combination of the mTOR inhibitor rapamycin and CC-5013 has synergistic activity in multiple myeloma. Blood 2004;104:4188-4193.
40. Frost P, Moatamed F, Hoang B, et al. In vivo antitumor effects of the mTOR inhibitor CCI-779 against human multiple myeloma cells in a xenograft model. Blood 2004;104:4181-4187.
41. Shi Y, Gera J, Hu L, et al. Enhanced sensitivity of multiple myeloma cells containing PTEN mutations to CCI-779. Cancer Res 2002;62:5027-5034.
42. Stromberg T, Dimberg, A, Hammarberg A, et al. Rapamycin sensitizes multiple myeloma cells to apoptosis induced by dexamethasone. Blood 2004;103:3138-3147.
43. Francis LK, Alsayed Y, Leleu X, et al. Combination mammalian target of rapamycin inhibitor rapamycin and HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin has synergistic activity in multiple myeloma. Clin Cancer Res 2006;12:6826-6835.
44. Feldman ME, Apsel B, Uotila A, et al. Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol 2009;7:e38.
45. Dowling RJ, Topisirovic I, Fonseca BD, et al. Dissecting the role of mTOR: Lessons from mTOR inhibitors. Biochim Biophys Acta 2010;1804:433-439.
46. Dowling RJ, Pollak M, Sonenberg N. Current status and challenges associated with targeting mTOR for cancer therapy. BioDrugs Clin Immunother Biopharm Gene Ther 2009;23:77-91.
47. Gupta M, Ansell SM, Novak AJ, et al. Inhibition of histone deacetylase overcomes rapamycin-mediated resistance in diffuse large B-cell lymphoma by inhibiting Akt signaling through mTORC2. Blood 2009;114:2926-2935.
48. Ansell SMTH, Kurtin PJ, Koenig PA, et al. Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma: A phase 2 study. Lancet Oncol 2011;12:361-368.
49. Roccaro AM, Sacco A, Husu EN, et al. Dual targeting of the PI3K/Akt/mTOR pathway as an antitumor strategy in Waldenstrom macroglobulinemia. Blood 2010;115:559-569.