Table 2 Clinical studies evaluating HDACis for the treatment of MM

NCT00445068

II

n = 38

Panobinostat

20 mg, Days 1, 3, 5, 8, 10, 12, every 21 days

ORR: 2.63%

Thrombocytopeni (50%), anemia (11.2%), neutropenia (8%), fatigue (26%)

[86]

NCT00621244

Ia/II

n = 176

Panobinostat

From 20-80 mg three times a week or once every 14 days

Not found

Thrombocytopenia (41.5%), neutropenia (21%), fatigue (21%)

[87]

NCT01720875

II

n = 16

Vorinostat/ Bortezomib/ Dexamethasone

400 mg, Days 1–14, every 21 days

ORR: 81.3%

Thrombocytopenia (50%), diarrhea (6.3%), fatigue (6.3%), anemia (6.3%)

[88]

NCT01583283

I

n = 38

ACY-1215/ Lenalidomide/ Dexamethasone

From 40–240 mg once daily to 160 mg twice daily

ORR: 55%

Fatigue (18%), diarrhea (5%)

[89]

NCT01502085

I/II

n = 25

Vorinostat/ Lenalinomide/ Dexamethasone

Vorinostat: 400 mg once a week; Lenalidomide: 25 mg once two weeks; Dexamethasone: 40 mg, Days 1, 8, 15 and 22

ORR: 24%

Thrombocytopenia (56%), fatigue (72%), diarrhea (72%), neutropenia (68%), vomiting (12%)

[90]

NCT00642954

I

n = 31

Vorinostat/ Lenalidomide/ Dexamethasone

Vorinostat: 400 m, days 1–7 and 15–21; Lenalidomide: 25 mg, days 1–21; Dexamethasone: 40 mg, Days 1, 8, 15, 22, every 28 days

ORR: 47%

Anemia (58%), thrombocytopenia (58%), diarrhea (55%), fatigue (55%), cough (45%)

[91]

NCT02290431

II

n = 31

Panobinostat/ Bortezomib/ Dexamethasone

20 mg, Days 1, 3, 5, 8, 10, 12, every 21 days

ORR: 80.6%

Thrombocytopenia (48.4%), fatigue (25.8%), diarrhea (22.6%), neutropenia (22.6%), lymphopenia (22.6%)

[93]

NCT01440582

I

n = 55

Panobinostat/ Bortezomib/ Lenalidomide/ Dexamethasone

Bortezomib: (1.3 mg/m²), Days 1, 4, 8, 11; Lenalidomide: 25 mg, Days 1–14; Dexamethasone: 20 mg, Days 1, 2, 4, 5, 8, 9, 11, 12

Not found

Thrombocytopenia (17%), diarrhea (17%)

[94]

NCT02654990

II

n = 248

Panobinostat/ Bortezomib/ Dexamethasone

82 to panobinostat 20 mg thrice weekly, 83 to panobinostat 20 mg twice weekly, and 83 to 10 mg panobinostat three times weekly

ORR: 62·2% (20 mg three times weekly group); 65·1% (20 mg twice weekly group), 50·6% (10 mg three times weekly group)

Thrombocytopenia (32%), neutropenia (15.2%), pneumonia (11.6%)

[95]

NCT01083602

II

n = 55

Panobinostat/ Bortezomib/ Dexamethasone

20 mg, Days 1, 3, 5, 8, 10, 12, every 21 days

ORR: 34.5%

Thrombocytopenia (63.6%), diarrhea (20%), fatigue (20%), anemia (14.5%), neutropenia (14.5%), pneumonia (14.5%)

[96]

NCT00773838

II

n = 143

Vorinostat/ Bortezomib/ Dexamethasone

400 mg, Days 1–14, every 21 days

ORR: 11.3%

Diarrhea (4.2%), asthenia (2.8%), thrombocytopenia ( 2.8%), pneumonia ( 2.1%), neuralgia (1.4%)

[97]

NCT00858234

I

n = 9

Vorinostat/ Bortezomib

400 mg, Days 1–14, every 21 days

ORR: 44%

Thrombocytopenia (100%), lymphopenia (43%), neutropenia (29%), anemia (29%), nausea (29%), dehydration (29%), pneumonia (29%), diarrhea (14%), decreased appetite (14%), fatigue (14%), hypokalemia (14%)

[101]

NCT01023308

III

n = 768

Panobinostat/ Bortezomib/ Dexamethasone/ Placebo

Panobinostat: 20 mg (hard gelatin capsules); Bortezomib: 1.3 mg/m2 as a 3 to 5 s bolus intravenous injection; Dexamethasone: 20 mg every day

ORR: 60.7%

Pneumonia (14.7%), thrombocytopenia (7.35%), diarrhea (11.29%) anemia (3.67%), vomiting (3.15%), asthenia (3.94%), fatigue (2.89%) pyrexia (4.20%),

[102]

NCT01549431

I

n = 32

Panobinostat/ Carfilzomib

20 mg, Days 1, 3, 5, 15, 17, 19, every 28 days

ORR: 63%

Thrombocytopenia (41%), fatigue (17%), nausea (12%), vomiting (12%)

[103]

NCT01496118

I/II

n = 80

Panobinostat/ Carfilzomib

20 mg, 30 mg, Days 1, 3, 5, 15, 17, 19, every 28 days

ORR: 84.4%

Thrombocytopenia (60.6%), fatigue (18.2%), anemia (12.1%), dyspnea (12.1%), diarrhea (9.1%), neutropenia (9.1%), nausea (6.1%), vomiting (6.1%), peripheral neuropathy (3%)

[104, 105]

NCT01464112

I

n = 18

JNJ-2641585 / VELCADE / Dexamethasone

JNJ-2641585: 10 mg three times weekly oral dose with VELCADE + Dexamethasone

ORR: 88.2%

Thrombocytopenia (61.1%), asthenia (55.6%), diarrhea (66.7%)

[110]

NCT00773747

III

n = 637

Vorinostat/ Bortezomib

400 mg, Days 1–14, every 21 days

ORR: 11.3%

Thrombocytopenia (45%), neutropenia (28%), anaemia (17%)

[111]

NCT00532389

Ib

n = 62

Panobinostat/ Bortezomib

Panobinostat 20 mg thrice weekly every week + Bortezomib 1.3 mg/m², every 21 days

ORR: 73.3%

Thrombocytopenia (85.1%), neutropenia (63.8%), asthenia (29.8%), fatigue (20.0%)

[112]

NCT00742027

II

n = 27

Panobinostat/ Lenalidomide/ Dexamethasone

20 mg, Days 1, 3, 5, 15, 17, 19, every 28 days

ORR: 41%

Neutropenia (59%), thrombocytopenia (31%), fatigue (12.5%), infection (15.6%), diarrhea (9.4%) anemia (5%)

[113]