Selected studies in dual-refractory or later myeloma
| Intervention (study name) . | N . | Prior lines or regimens, median (range), n . | ORR (%) . | VGPR or better (%) . | CR or better (%) . | Refractory population* . | PFS HR† or RR in Refractory Population . | PFS HR† or RR in high risk‡ . | Median PFS (mo) . | Median OS (mo) . |
|---|---|---|---|---|---|---|---|---|---|---|
| dara/pom/dex (EQUUELEUS)48 | 103 | 4 (1-13) | 60 | 42 | 17 | 71% dual | 58% | 59% | 8.8 | 17.5 |
| dara/cfz/dex49 | 85 | 2 (1-4) | 84 | 71 | 33 | 60% to len | 79% in len ref | 69% | NR | NR |
| 29% dual | ||||||||||
| dara50 | 42 | 4 (2-12) | 36 | 10 | 5 | 64% dual | 33% in dual | NG | 5.6 | NG |
| 48% triple | 30% in triple | |||||||||
| 19% quad | 38% in quad | |||||||||
| dara/dex (SIRIUS)18 | 106 | 5 (2-14) | 29 | 9 | 3 | 82% dual | 26% dual | 20% | 3.7 | 17.5 |
| 66% triple | 29% in triple | |||||||||
| 31% quad | 21% in quad | |||||||||
| elo/pom/dex vs pom/dex (ELOQUENT-3)51 | 60 vs 57 | 3 (2-8) | 53 vs 26 | 20 vs 9 | 8 vs 2 | 68% vs 72% dual (PI+len) | 0.56 (0.33-0.97) | 0.55 (0.28-1.10) | 10.3 vs 4.7 | NG |
| cfz 70 qweek/dex vs cfz 27 biweek/dex (ARROW)52 | 240 vs 238 | 2 (2-3) | 63 vs 41 | 34 vs 13 | 7 vs 2 | 42% to btz | 0.76 (0.58-0.99) in len ref | 0.55 (0.30-1.03) | 11.2 vs 7.6 | NG |
| 92% to IMID | 0.73 (0.51-1.05) in btz ref | |||||||||
| cfz/pom/dex53 | 32 | 6 (2-12) | 50 | 16 | 0 | 100% to len | 50% in dual | 80% in del(17p) | 7.2 | 20.6 |
| 91% dual (to btz+len) | ||||||||||
| cfz/pom/dex54 | 47 | 2 (1-3) | 62 | 19 | 2 | 100% to len | 71% in dual | 40% | 10.3 | NG |
| 45% dual (to btz+len) | ||||||||||
| ixa/pom/dex55 | 25 | 2 (1-5) | 48 | 20 | 0 | 100% to len | 29% in dual | 56% | 8.6 | NG |
| 56% dual (to btz+len) | ||||||||||
| Pom/dex vs high dex (MM-003)56 | 302 vs 153 | 5 (2-17) | 31 vs 10 | 5 vs <1 | 1 vs 0 | 94% to len | 0.52 (0.41-0.68) in dual | 0.46 (0.30-0.72) | 4.0 vs 1.9 | 12.7 vs 8.1 |
| 74% dual (to btz+len) | ||||||||||
| Pom/dex (MM-010)57 | 682 | 5 (2-18) | 32.6 | 7.6 | 0.6 | 96% to len | 32% in len ref | NG | 4.6 | 11.9 |
| 84% to btz | 33% in btz ref | |||||||||
| 80% dual (to btz+len) | 32% in dual | |||||||||
| Cyclophosphamide/len/pred (REPEAT)58 | 82 | 3 (1-10) | 67 | 23 | 4.5 | 100% to len | 60% in dual | 67% | 12.1 | 29.0 |
| 66% dual (to btz+len) | ||||||||||
| Cyclophosphamide/pom/dex59 | 34 | 4 (2-9) | 65 | 12 | 3 | 100% dual (to PI+len) | 65% | NG | 9.5 | NG |
| pano/btz/dex (PANORAMA 2)61 | 55 | 4 (2-11) | 34.5 | 2 | 0 | 100% to btz | 34.5% | 43% | 5.4 | NG |
| 100% IMID exp |
| Intervention (study name) . | N . | Prior lines or regimens, median (range), n . | ORR (%) . | VGPR or better (%) . | CR or better (%) . | Refractory population* . | PFS HR† or RR in Refractory Population . | PFS HR† or RR in high risk‡ . | Median PFS (mo) . | Median OS (mo) . |
|---|---|---|---|---|---|---|---|---|---|---|
| dara/pom/dex (EQUUELEUS)48 | 103 | 4 (1-13) | 60 | 42 | 17 | 71% dual | 58% | 59% | 8.8 | 17.5 |
| dara/cfz/dex49 | 85 | 2 (1-4) | 84 | 71 | 33 | 60% to len | 79% in len ref | 69% | NR | NR |
| 29% dual | ||||||||||
| dara50 | 42 | 4 (2-12) | 36 | 10 | 5 | 64% dual | 33% in dual | NG | 5.6 | NG |
| 48% triple | 30% in triple | |||||||||
| 19% quad | 38% in quad | |||||||||
| dara/dex (SIRIUS)18 | 106 | 5 (2-14) | 29 | 9 | 3 | 82% dual | 26% dual | 20% | 3.7 | 17.5 |
| 66% triple | 29% in triple | |||||||||
| 31% quad | 21% in quad | |||||||||
| elo/pom/dex vs pom/dex (ELOQUENT-3)51 | 60 vs 57 | 3 (2-8) | 53 vs 26 | 20 vs 9 | 8 vs 2 | 68% vs 72% dual (PI+len) | 0.56 (0.33-0.97) | 0.55 (0.28-1.10) | 10.3 vs 4.7 | NG |
| cfz 70 qweek/dex vs cfz 27 biweek/dex (ARROW)52 | 240 vs 238 | 2 (2-3) | 63 vs 41 | 34 vs 13 | 7 vs 2 | 42% to btz | 0.76 (0.58-0.99) in len ref | 0.55 (0.30-1.03) | 11.2 vs 7.6 | NG |
| 92% to IMID | 0.73 (0.51-1.05) in btz ref | |||||||||
| cfz/pom/dex53 | 32 | 6 (2-12) | 50 | 16 | 0 | 100% to len | 50% in dual | 80% in del(17p) | 7.2 | 20.6 |
| 91% dual (to btz+len) | ||||||||||
| cfz/pom/dex54 | 47 | 2 (1-3) | 62 | 19 | 2 | 100% to len | 71% in dual | 40% | 10.3 | NG |
| 45% dual (to btz+len) | ||||||||||
| ixa/pom/dex55 | 25 | 2 (1-5) | 48 | 20 | 0 | 100% to len | 29% in dual | 56% | 8.6 | NG |
| 56% dual (to btz+len) | ||||||||||
| Pom/dex vs high dex (MM-003)56 | 302 vs 153 | 5 (2-17) | 31 vs 10 | 5 vs <1 | 1 vs 0 | 94% to len | 0.52 (0.41-0.68) in dual | 0.46 (0.30-0.72) | 4.0 vs 1.9 | 12.7 vs 8.1 |
| 74% dual (to btz+len) | ||||||||||
| Pom/dex (MM-010)57 | 682 | 5 (2-18) | 32.6 | 7.6 | 0.6 | 96% to len | 32% in len ref | NG | 4.6 | 11.9 |
| 84% to btz | 33% in btz ref | |||||||||
| 80% dual (to btz+len) | 32% in dual | |||||||||
| Cyclophosphamide/len/pred (REPEAT)58 | 82 | 3 (1-10) | 67 | 23 | 4.5 | 100% to len | 60% in dual | 67% | 12.1 | 29.0 |
| 66% dual (to btz+len) | ||||||||||
| Cyclophosphamide/pom/dex59 | 34 | 4 (2-9) | 65 | 12 | 3 | 100% dual (to PI+len) | 65% | NG | 9.5 | NG |
| pano/btz/dex (PANORAMA 2)61 | 55 | 4 (2-11) | 34.5 | 2 | 0 | 100% to btz | 34.5% | 43% | 5.4 | NG |
| 100% IMID exp |
biweek, days 1, 2, 8, 9, 15, and 16 out of every 28 days; elo, elotuzumab; exp, exposed; NG, not given; NR, not reached; ORR, overall response rate; pano, panobinostat; pom, pomalidomide; pred, prednisone; qweek, days 1, 8, and 15 out of every 28 days; ref, refractory; RR, response rate.
Not all studies reported refractoriness. Some reported the number of patients previously exposed; for these studies, prior exposure is indicated with “exp.”
Where given, HR reflects the novel agent arm (frequently a triplet) compared with the control arm (frequently a doublet).
Note that studies differed in their definitions of high-risk disease.