Table 2.
Selected Clinical Trials of Non- HDAC inhibitor Combination Therapies with Hypomethylating Agents in MDS
| Study | Intervention | Design | N | Med Age |
% MDS |
ORR%* | CR/PR/HI* | Med OS (ms) |
|---|---|---|---|---|---|---|---|---|
| Sekeres et al 2012 |
AZA + LEN | Phase II |
36 | 68 | 100% | 72% | 44% | 13.6 |
| Narayan et al 2015 |
AZA + LEN | Phase II |
32 | 73.5 | 19% | 25% | 12.5% | 5 |
| DiNardo et al 2015 |
AZA + LEN | Phase I/II |
88 | 67 | 51% | 35% | 17% | 32.8 |
| Sekeres et al 2015 |
AZA AZA + LEN |
Phase II, RCT |
Total, n=277 AZA, n=92 AZA + LEN, n= 93 |
- | 100% |
AZA 37% AZA + LEN 45% [p vs AZA= 0.45] |
AZA 24% AZA + LEN 21% [p vs AZA = 0.73] |
AZA 15 AZA + LEN 18 [p vs AZA = 0.38] |
| Mittelman et al 2013 |
AZA + LEN | Phase 2 | 18 | - | 100% HR and LR MDS Selected for 5q- |
78% | 44% | - |
| Platzbecker et al 2013 |
AZA + LEN | Phase I | 19 | 69 | 65% Selected for 5q- |
42% | 11% | |
| Ades et al 2015 |
AZA + LEN | Phase I-II |
49 | 69 | 63% IPSS-2 or high risk MDS Selected for 5q- |
24% | 8.2% | - |
| Itzykson et al 2012 |
AZA + ESA | Retro. | Total, n= 282 AZA, n= 239 AZA + ESA, n= 32 |
72 | Total 77% AZA 84% AZA + ESA 76% |
AZA 43% AZA + ESA 53 % [p vs AZA= 0.34] |
AZA 13% AZA +ESA 19% |
AZA 11.9 AZA + ESA 19.6 [p vs AZA = 0.04] |
| Tobiasson et al 2014 |
AZA + ESA | Phase II |
Total, n=30 AZA, n= 30 AZA + ESA, n=16 |
69 | 100% IPSS low and Int-1 refractory to ESA |
AZA 23% AZA + ESA 7% |
- | - |
| Kantarjian et al 2010 |
AZA + ROM | Phase II, RCT |
Total, n= 40 AZA, n= 13 AZA + ROM 500µg , n= 13 AZA + ROM 750µg, n= 14 |
71 | 100% IPSS Low, Int-1, Int-2 |
AZA 15% AZA + ROM 500µg 8% AZA + ROM 750µg 14% |
-- | |
| Greenberg et al 2013 |
ROM + DAC |
Phase II, RCT |
Total, n=29 DAC, n= 14 DAC + ROM, n=15 |
68 | 100% IPSS low, Int, high risk MDS |
DAC 21% DAC + ROM 33% ** Non- significant |
DAC 7% DAC + ROM 13%** Non- significant |
- |
| Svensson et al 2014 |
ELT + AZA | Phase I | 12 | 74 | 100% | 67% | 33% | - |
| Strati et al 2015 |
MID + AZA | Phase I/II |
54 | 65 | 5% | 26% | 2% | 5.5 |
| Daver et al 2015 |
GEM + AZA | Phase II | 110 | 70 | 22% | - | 35% | 5.7 |
| Fathi et al 2015 |
SGN-33A + HMA |
Phase 1 | 23 | 77 | 0% MDS 100% AML |
65% | 22% | - |
| Ravandi et al 2012 |
SAP + DAC | Phase I/II/III |
33 | 77 | 0% MDS 100% AML |
37% | 30% | 7.8 |
| Nevada et al 2014 |
RIG + AZA | Phase I/II |
18 12 Evaluable |
70.5 | 61% | 50% | 8.3% | - |
| Tibes et al 2015 |
SON + AZA | Phase I/ Ib |
29 | 72 | 31% | - | 40% | - |
| Ritchie et al 2015 |
BIR + AZA | Phase II |
6 | ≥ 60 | 100% | 83% | 50% | - |
Abbreviations: AZA, azacitidine; DAC, decitabine; HMA, hypomethylating agent; LEN, lenalidomide; GEM, gemtuzumab; ESA, erythrocyte stimulating agent; ELT, eltrombopag; MID, midostaurin; SGN-33A, SGN-CD33A; SAP, sapacitabine; RIG, rigosertib; SON, sonidegib; BIR, birinapant; Retro, retrospective study; ms, months, ORR, overall response rate; CR, complete remission; Med, median; N, number of study participants;