Deacetylase inhibitors as a novel modality in the treatment of multiple myeloma

Pharmacological Research

Volumn 117, Issue , 2017, Pages 185-191

  Richardson, Paul G ^a   Moreau, Philippe ^b   Laubach, Jacob P ^a   Maglio, Michelle E ^a   Lonial, Sagar ^c   San Miguel, Jesus ^d  

^a HARVARD MEDICAL SCHOOL   (United States)

^b NANTES UNIVERSITY HOSPITAL   (France)

^c EMORY UNIVERSITY   (United States)

^d UNIVERSITY CLINIC OF NAVARRA   (Spain)

Author keywords

Epigenetic modification; Histone deacetylase inhibitors; Multiple myeloma

Indexed keywords

BORTEZOMIB; CARFILZOMIB; CITARINOSTAT; DEXAMETHASONE; HISTONE DEACETYLASE; HISTONE DEACETYLASE INHIBITOR; LENALIDOMIDE; PANOBINOSTAT; PLACEBO; POMALIDOMIDE; RICOLINOSTAT; ROMIDEPSIN; VORINOSTAT; ANTINEOPLASTIC AGENT; HYDROXAMIC ACID; INDOLE DERIVATIVE;

AGGRESOME; ANEMIA; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ASTHENIA; AUTOPHAGOSOME; AUTOPHAGY; CANCER RECURRENCE; CANCER SURVIVAL; CARDIOTOXICITY; CELL CYCLE PROGRESSION; CELL GROWTH; CELL SURVIVAL; CONGESTIVE HEART FAILURE; COUGHING; DECREASED APPETITE; DIARRHEA; DRUG ABSORPTION; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG ELIMINATION; DRUG HALF LIFE; DRUG METABOLISM; DRUG POTENCY; DRUG RESPONSE; DRUG WITHDRAWAL; DYSPNEA; ENZYME INHIBITION; EPIGENETICS; EPISTAXIS; FATIGUE; FEBRILE NEUTROPENIA; GASTROINTESTINAL TOXICITY; HEMATOLOGIC DISEASE; HUMAN; HYPERGLYCEMIA; HYPERTENSION; HYPERTRANSAMINASEMIA; HYPOKALEMIA; HYPONATREMIA; HYPOPHOSPHATEMIA; IMMUNOMODULATION; LEUKOPENIA; LUNG INFECTION; LYMPHOCYTOPENIA; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; NAUSEA; NEUTROPENIA; OVERALL SURVIVAL; PERIPHERAL NEUROPATHY; PNEUMONIA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEIN DEGRADATION; QT PROLONGATION; REVIEW; SINGLE DRUG DOSE; SUPRAVENTRICULAR TACHYCARDIA; THROMBOCYTOPENIA; VOMITING;

ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BORTEZOMIB; DEXAMETHASONE; HISTONE DEACETYLASE INHIBITORS; HUMANS; HYDROXAMIC ACIDS; INDOLES; MULTIPLE MYELOMA;

EID: 85007518472     PISSN: 10436618     EISSN: 10961186     Source Type: Journal    
DOI: 10.1016/j.phrs.2016.11.020     Document Type: Review

References (42)

1. [1] Bolden, J.E., Peart, M.J., Johnstone, R.W., Anticancer activities of histone deacetylase inhibitors. Nat. Rev. Drug Discov. 5 (2006), 769–784.
2. [2] Choudhary, C., Kumar, C., Gnad, F., Nielsen, M.L., Rehman, M., Walther, T.C., et al. Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325 (2009), 834–840.
3. [3] West, A.C., Johnstone, R.W., New and emerging HDAC inhibitors for cancer treatment. J. Clin. Invest. 124 (2014), 30–39.
4. [4] Gryder, B.E., Sodji, Q.H., Oyelere, A.K., Targeted cancer therapy: giving histone deacetylase inhibitors all they need to succeed. Future Med. Chem. 4 (2012), 505–524.
5. [5] Stimson, L., Wood, V., Khan, O., Fotheringham, S., La Thangue, N.B., HDAC inhibitor-based therapies and haematological malignancy. Ann. Oncol. 20 (2009), 1293–1302.
6. [6] Gregoretti, I.V., Lee, Y.M., Goodson, H.V., Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. J. Mol. Biol. 338 (2004), 17–31.
7. [7] Dawson, M.A., Kouzarides, T., Cancer epigenetics: from mechanism to therapy. Cell 150 (2012), 12–27.
8. [8] Mithraprabhu, S., Kalff, A., Chow, A., Khong, T., Spencer, A., Dysregulated Class I histone deacetylases are indicators of poor prognosis in multiple myeloma. Epigenetics 9 (2014), 1511–1520.
9. [9] Kawaguchi, Y., Kovacs, J.J., McLaurin, A., Vance, J.M., Ito, A., Yao, T.P., The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 115 (2003), 727–738.
10. [10] Atadja, P., Development of the pan-DAC inhibitor panobinostat (LBH589): successes and challenges. Cancer Lett. 280 (2009), 233–241.
11. [11] Heise, C., Presented At: 4th Annual HDAC Inhibitors Meeting, Boston, Massachusetts, 2010 (abstract).
12. [12] San-Miguel, J.F., Hungria, V.T., Yoon, S.S., Beksac, M., Dimopoulos, M.A., Elghandour, A., et al. Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial. Lancet Oncol. 15:11 (2014), 1195–1206.
13. [13] Dimopoulos, M., Siegel, D.S., Lonial, S., Qi, J., Hajek, R., Facon, T., et al. Vorinostat or placebo in combination with bortezomib in patients with multiple myeloma (VANTAGE 088): a multicentre, randomised, double-blind study. Lancet Oncol. 14 (2013), 1129–1140.
14. [14] Harada, T., Hideshima, T., Anderson, K.C., Histone deacetylase inhibitors in multiple myeloma: from bench to bedside. Int. J. Hematol. 104 (2016), 300–309.
15. [15] Santo, L., Hideshima, T., Kung, A.L., Tseng, J.C., Tamang, D., Yang, M., et al. Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma. Blood 119 (2012), 2579–2589.
16. [16] Libby, E.N., Becker, P.S., Burwick, N., Green, D.J., Holmberg, L., Bensinger, W.I., Panobinostat: a review of trial results and future prospects in multiple myeloma. Expert Rev. Hematol. 8 (2015), 9–18.
17. [17] Hideshima, T., Richardson, P.G., Anderson, K.C., Mechanism of action of proteasome inhibitors and deacetylase inhibitors and the biological basis of synergy in multiple myeloma. Mol. Cancer Ther. 10 (2011), 2034–2042.
18. [18] Ocio, E.M., Vilanova, D., Atadja, P., Maiso, P., Crusoe, E., Fernandez-Lazaro, D., et al. In vitro and in vivo rationale for the triple combination of panobinostat (LBH589) and dexamethasone with either bortezomib or lenalidomide in multiple myeloma. Haematologica 95 (2010), 794–803.
19. [19] Clive, S., Woo, M.M., Nydam, T., Kelly, L., Squier, M., Kagan, M., Characterizing the disposition, metabolism, and excretion of an orally active pan-deacetylase inhibitor, panobinostat, via trace radiolabeled 14C material in advanced cancer patients. Cancer Chemother. Pharmacol. 70 (2012), 513–522.
20. [20] San-Miguel, J.F., Richardson, P.G., Gunther, A., Sezer, O., Siegel, D., Blade, J., et al. Phase Ib study of panobinostat and bortezomib in relapsed or relapsed and refractory multiple myeloma. J. Clin. Oncol. 31 (2013), 3696–3703.
21. [21] Raje, N., Vogl, D., Hari, P., Jagannath, S., Jones, S., Supko, J., et al. ACY-1215, a selective histone deacetylase (HDAC) 6 inhibitor: interim results of combination therapy with bortezomib in patients with multiple myeloma (MM). Blood, 122(21), 2013 (abstract 759).
22. [22] Vogl, D.T., Raje, N.S., Jagannath, S., Richardson, P.G., Hari, P., Orlowski, R.Z., et al. Ricolinostat (ACY-1215), the first selective HDAC6 inhibitor, in combination with bortezomib and dexamethasone in patients with relapsed or relapsed-and-refractory multiple myeloma: phase 1b results (ACY-100 Study). Blood, 126, 2015, 1827.
23. [23] Yee, A.J., Voorhees, P.M., Bensinger, W., Berdeja, J.G., Supko, J.G., Richardson, P.G., et al. Ricolinostat (ACY-1215), a selective HDAC6 inhibitor, in combination with lenalidomide and dexamethasone: results of a phase 1b trial in relapsed and relapsed refractory multiple myeloma. Blood (ASH Annual Meeting Abstracts), 124, 2014 (abstract 4772).
24. [24] Yee, A.J., Bensinger, W.I., Supko, J.G., Voorhees, P.M., Berdeja, J.G., Richardson, P., et al. Ricolinostat plus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: a multicentre phase 1b trial. Lancet Oncol. 17:11 (2016), 1569–1578.
25. [25] Raje, N., Bensinger, W., Cole, C., Lonial, S., Jagannath, S., Arce-Lara, C., et al. Ricolinostat (ACY-1215), the first selective HDAC6 inhibitor, combines safely with pomalidomide and dexamethasone and shows promising early results in relapsed-and-refractory myeloma (ACE-MM-102 Study). Blood, 126, 2015 (abstract 4228).
26. [26] Yee, A., Vorhees, P., Bensinger, W., Berdeja, J.G., Supko, J., Richardson, P., et al. ACY-1215, a selective histone deacetylase (HDAC) 6 inhibitor, in combination with lenalidomide and dexamethasone (dex), is well tolerated without dose limiting toxicity (DLT) in patients (Pts) with multiple myeloma (MM) at doses demonstrating biologic activity: interim results of a phase 1b trial. Blood, 122(21), 2013 [abstract 3190].
27. [27] San-Miguel, J., Hungria, V., Yoon, S., Beksac, M., Dimopoulos, M., Elghandour, A., et al. Final analysis of overall survival from the phase 3 PANORAMA 1 trial of panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma. ASH Annual Meeting, 2015 (abstract 3026).
28. [28] Richardson, P.G., Hungria, V.T., Yoon, S.S., Beksac, M., Dimopoulos, M.A., Elghandour, A., et al. Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma: outcomes by prior treatment. Blood 127 (2016), 713–721.
29. [29] Moreau, P., Pylypenko, H., Grosicki, S., Karamanesht, I., Leleu, X., Grishunina, M., et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol. 12 (2011), 431–440.
30. [30] Bringhen, S., Larocca, A., Rossi, D., Cavalli, M., Genuardi, M., Ria, R., et al. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood 116 (2010), 4745–4753.
31. [31] Richardson, P.G., Schlossman, R.L., Alsina, M., Weber, D.M., Coutre, S.E., Gasparetto, C., et al. PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood 122 (2013), 2331–2337.
32. [32] Richardson, P.G., Schlossman, R.L., Alsina, M., Weber, D.M., Coutre, S.E., Gasparetto, C., et al. Time to event analyses in PANORAMA 2: a phase 2 study of panobinostat, bortezomib, and dexamethasone in patients with relpased and bortezomib-refractory multiple myeloma ASH. Annu. Meeting, 122(21), 2013, 1970 (abstract 1970).
33. [33] Berdeja, J.G., Gregory, T.B., Faber, E.A., Matous, J.V., Hart, L.L., Mace, J.R., et al. A phase I/II study of the combination of panobinostat (PAN) and carfilzomib (CFZ) in patients (pts) with relapsed/refractory multiple myeloma (MM): comparison of two expansion cohorts. Blood, 126, 2015 (abstract 1825).
34. [34] Shah, J.J., Thomas, S.K., Weber, D.M., Wang, M., Alexanian, R., Qazilbash, M.H., et al. Phase 1/1b study of the efficacy and safety of the combination of panobinostat + carfilzomib in patients with relapsed and/or refractory multiple myeloma. ASH Annual Meeting, 120, 2012 (abstract 4081).
35. [35] Kaufman, J., Zimmerman, T., Rosenbaum, C., Nooka, A., Heffner, L.J., Harvey, R., et al. Phase I study of the combination of carfilzomib and panobinostat for patients with relapsed and refractory myeloma: a Multiple Myeloma Research Consortium (MMRC) clinical trial. Blood, 124, 2014 (abstract 32).
36. [36] Siegel, D.S., Richardson, P., Dimopoulos, M., Moreau, P., Mitsiades, C., Weber, D., et al. Vorinostat in combination with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. Blood Cancer J., 4, 2014, e182.
37. [37] Chari, A., Cho, H., Leng, S., Dhadwal, A., Morgan, G., La, L., et al. A phase II study of panobinostat with lenalidomide and weekly dexamethasone in myeloma. Blood, 126, 2015 (abstract 4226).
38. [38] Niesvizky, R., Richardson, P., Gabrail, N., Madan, S., Yee, A.J., Shain, K., et al. ACY-241, a novel, HDAC6 selective inhibitor: synergy with immunomodulatory (IMiD) drugs in multiple myeloma (MM) cells and early clinical results (ACE-MM-200 Study). Blood, 126, 2015 (abstract 3040).
39. [39] Laubach, J., Tuchman, S., Rosenblatt, J., Redd, R., Colson, K., Motta, A., et al. Phase 1b study of panobinostat in combination with lenalidomide, bortezomib, and dexamethasone in relapsed refractory multiple myeloma. ASCO Meeting Abstracts, 34, 2016, 8014.
40. [40] Shah, J.J., Feng, L., Manasanch, E.E., Weber, D., Thomas, S.K., Turturro, F., et al. Phase I/II trial of the efficacy and safety of combination therapy with lenalidomide/bortezomib/dexamethasone (RVD) and panobinostat in transplant-eligible patients with newly diagnosed multiple myeloma. Blood, 126, 2015 (abstract 187).
41. [41] Lee, A.J., Bensinger, W.I., Supko, J.G., Voorhees, P.M., Berdeja, J.G., Richardson, P.G., et al. Ricolinostat plus lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: a multicentre phase 1b trial. Lancet Oncol. 17 (2016), 1569–1578.
42. [42] Laubach, J.P., Voorhees, P.M., Hassoun, H., Jakubowiak, A., Lonial, S., Richardson, P.G., Current strategies for treatment of relapsed/refractory multiple myeloma. Expert Rev. Hematol. 7 (2014), 97–111.