Phase II study of melphalan, thalidomide and prednisone
combined with oral panobinostat in patients with relapsed/refractory multiple
Leuk Lymphoma. 2012 Sep;53(9):1722-7.
Offidani M, Polloni C, Cavallo F, Liberati AM, Ballanti S, Pulini S, Catarini M,
Alesiani F, Corvatta L, Gentili S, Caraffa P, Boccadoro M, Leoni P, Palumbo A.
Response rate of MPT + panobinostat in relapsed/refractory myeloma was 38%.
Phase II trial of the pan-deacetylase inhibitor panobinostat
as a single agent in advanced relapsed/refractory multiple myeloma.
Leuk Lymphoma. 2012 Sep;53(9):1820-3.
Wolf JL, Siegel D, Goldschmidt H, Hazell K, Bourquelot PM, Bengoudifa BR, Matous
J, Vij R, de Magalhaes-Silverman M, Abonour R, Anderson KC, Lonial S.
Only 1 partial response was observed among 38 patients treated with
PANORAMA 2: panobinostat in combination with bortezomib and
dexamethasone in patients with relapsed and bortezomib-refractory myeloma.
Blood. 2013 Oct 3;122(14):2331-7.
Richardson PG, Schlossman RL, Alsina M, Weber DM, Coutre SE, Gasparetto C,
Mukhopadhyay S, Ondovik MS, Khan M, Paley CS, Lonial S.
Among 55 patients with relapsed and bortezomib-refractory myeloma, clinical
benefit rate of panobinostat + bortezomib + dexamethasone was 53% (10 minimal
responses, 18 partial responses, and 1 near-CR). Median progression-free
survival was 5.4 months.
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
Lancet Oncol. 2014 Oct;15(11):1195-206.
San-Miguel JF, Hungria VT, Yoon SS, Beksac M, Dimopoulos MA, Elghandour A,
Jedrzejczak WW, Günther A, Nakorn TN, Siritanaratkul N, Corradini P,
Chuncharunee S, Lee JJ, Schlossman RL, Shelekhova T, Yong K, Tan D, Numbenjapon
T, Cavenagh JD, Hou J, LeBlanc R, Nahi H, Qiu L, Salwender H, Pulini S, Moreau
P, Warzocha K, White D, Bladé J, Chen W, de la Rubia J, Gimsing P, Lonial S,
Kaufman JL, Ocio EM, Veskovski L, Sohn SK, Wang MC, Lee JH, Einsele H, Sopala M,
Corrado C, Bengoudifa BR, Binlich F, Richardson PG.
Panobinostat is a pan-deacetylase inhibitor. This study, called PANORAMA1,
randomized 768 patients with relapsed/refractory multiple myeloma (s/p 1-3
previous treatment regimens) into two groups: the first one received bortezomib
+ dexamethasone + placebo (381), the second bortezomib + dexamethasone +
panobinostat 20 mg PO on days 1, 3, 5, 8, 10, 12 (387 patients). Results showed
a modest benefit from panobinostat:
- Response rate: similar (55% with placebo, and 61% with panobinostat,
- Rate of CR/nCR: 16% with placebo, and 28% with panobinostat (p<0.01)
- Median progression-free survival (primary endpoint): 8.1
months with placebo, and 12 months with panobinostat
- Median overall survival: similar (30.4 months with placebo, and 33.6
months with panobonostat, p=0.09; but median follow-up was approximately 6
Phase I/II study of the combination of panobinostat and
carfilzomib in patients with relapsed/refractory multiple myeloma.
Haematologica. 2015 May;100(5):670-6.
Berdeja JG, Hart LL, Mace JR, Arrowsmith ER, Essell JH, Owera RS, Hainsworth JD,
In this study, 44 patients with myeloma relapsed after at least one line of
therapy were treated with carfilzomib + panobinostat. Optimal doses were 20/45
mg/m2 for carfilzomib, and 30 mg for panobinostat. The response rate was 67% for
all patients. At a median follow up of 17 months, median overall survival was
not reached, and median progression-free survival was 8 months.
Phase I trial of oral vorinostat (suberoylanilide hydroxamic
acid, SAHA) in patients with advanced multiple myeloma.
Leuk Lymphoma. 2008 Mar;49(3):502-7.
Richardson P, Mitsiades C, Colson K, Reilly E, McBride L, Chiao J, Sun L, Ricker
J, Rizvi S, Oerth C, Atkins B, Fearen I, Anderson K, Siegel D.
13 patients with relapsed/refractory myeloma were enrolled in a phase I trial
of vorinostat 200, 250 or 300 mg PO bid for 5 days/week every 28 days or for 14
days every 21 days, continued until progressive disease or intolerable toxicity.
MTD was not determined due to early study termination. Of 10 evaluable patients,
there were 1 minimal response and 9 stable disease.
Vorinostat or placebo in combination with bortezomib in
patients with multiple myeloma (VANTAGE 088): a multicentre, randomised,
Lancet Oncol. 2013 Oct;14(11):1129-1140.
Dimopoulos M, Siegel DS, Lonial S, Qi J, Hajek R, Facon T, Rosinol L, Williams
C, Blacklock H, Goldschmidt H, Hungria V, Spencer A, Palumbo A, Graef T, Eid JE,
Houp J, Sun L, Vuocolo S, Anderson KC.
317 patients with relapsed (but non-refractory) myeloma were randomized to
bortezomib + vorinostat vs bortezomib + placebo. The vorinostat arm had a
statistically significant prolongation of median progression-free survival, but
this was not significant from the clinical point of view (7.6 vs 6.8 months, p=
A phase II multiple dose clinical trial of histone
deacetylase inhibitor ITF2357 in patients with relapsed or progressive multiple
Ann Hematol. 2010 Feb;89(2):185-90.
Galli M, Salmoiraghi S, Golay J, Gozzini A, Crippa C, Pescosta N, Rambaldi A.
ITF2357, an oral histone deacetylase inhibitor, was administered to 19
patients with advanced multiple myeloma in relapse or progression. 5 patients
had stable disease, and 14 had disease progression.
Ricolinostat plus lenalidomide, and dexamethasone in relapsed
or refractory multiple myeloma: a multicentre phase 1b trial.
Lancet Oncol. 2016 Nov;17(11):1569-1578.
Yee AJ, Bensinger WI, Supko JG, Voorhees PM, Berdeja JG, Richardson PG, Libby
EN, Wallace EE, Birrer NE, Burke JN, Tamang DL, Yang M, Jones SS, Wheeler CA,
Markelewicz RJ, Raje NS.
In this study, 38 patients with relapsed/refractory myeloma received
treatment with lenalidomide, dexamethasone, and ricolinostat, an oral histone
deacetylase (HDAC) inhibitor. Since it was a phase 1b trial, its goal was not to
assess antitumor efficacy. However, a preliminary analysis of the data showed a
response rate of 55%.
Ricolinostat, the First Selective Histone Deacetylase 6
Inhibitor, in Combination with Bortezomib and Dexamethasone for Relapsed or
Refractory Multiple Myeloma.
Clin Cancer Res. 2017 Jul 1;23(13):3307-3315.
Vogl DT, Raje N, Jagannath S, Richardson P, Hari P, Orlowski R, Supko JG, Tamang
D, Yang M, Jones SS, Wheeler C, Markelewicz RJ, Lonial S.
Ricolinostat is a selective HDAC inhibitor. In this trial, single
-agent ricolinostat did not induce responses in patients with
relapsed/refractory myeloma. In combination with bortezomib and dexamethasone,
the response rate was 37% (14% in patients previously refractory to bortezomib).
Phase 2 trial of the histone deacetylase inhibitor romidepsin
for the treatment of refractory multiple myeloma.
Cancer. 2011 Jan 15;117(2):336-42.
Niesvizky R, Ely S, Mark T, Aggarwal S, Gabrilove JL, Wright JJ, Chen-Kiang S,
This is a phase 2 trial of romidepsin in 12 patients with multiple myeloma.
Four of 12 patients had stable disease, but no patients had an objective
A high rate of durable responses with romidepsin, bortezomib,
and dexamethasone in relapsed or refractory multiple myeloma.
Blood. 2011 Dec 8;118(24):6274-83.
Harrison SJ, Quach H, Link E, Seymour JF, Ritchie DS, Ruell S, Dean J,
Januszewicz H, Johnstone R, Neeson P, Dickinson M, Nichols J, Prince HM.
Among 25 patients with relapsed/refractory myeloma, the combination of
bortezomib, dexamethasone, and romidepsine produced a response rate of 72% and a
median time to progression of about 7 months. Of note, only 24% of patients were
previously treated with a bortezomib-containing regimen.
Giampaolo Talamo, M.D.