Selected studies in early relapsed/single refractory myeloma
| Intervention (study name) . | N . | Prior lines or regimens, median (range), n . | ORR (%) . | VGPR or better (%) . | CR or better (%) . | Refractory population* . | PFS HR (95% CI) † or RR in refractory population . | PFS HR† or RR in high risk‡ . | Median PFS (mo) . | Median OS (mo) . |
|---|---|---|---|---|---|---|---|---|---|---|
| Refractory to IMID | ||||||||||
| ixa/len/dex vs pbo/len/dex (TOURMALINE-MM1)26,27 | 360 vs 362 | 1 (1-3) | 78 vs 72 | 48 vs 39 | 12 vs 7 | 55% IMID exp | 0.74 (0.54-1.03) in IMID exp | 0.54 (0.32-0.92) | 20.6 vs 14.7 | NG |
| 12% to thal | 0.73 (0.37-1.44) in thal ref | |||||||||
| ixa/dex28 | 35 | 4 (2-8) | 31 | 23 | 3 | 46% to len | 31% | 20% | 8.4 | NG |
| cfz/dex vs btz/dex (ENDEAVOR)30 | 464 vs 465 | 2 (1-2) | 77 vs 63 | 54 vs 29 | 13 vs 6 | 25% to len | 0.80 (0.57-1.11) | 0.65 (0.45-0.92) | 18.7 vs 9.4 | 47.6 vs 40.0 |
| cfz/len/dex vs len/dex (ASPIRE)31,32 | 396 vs 396 | 2 (1-3) | 87 vs 67 | 70 vs 40 | 32 vs 9 | 22% to IMID | 0.64 (0.44-0.91) | 0.70 (0.43-1.16) | 26.3 vs 17.6 | 48.3 vs 40.4 |
| dara/btz/dex vs btz/dex (CASTOR)33 | 251 vs 247 | 2 (1-10) | 84 vs 63 | 62 vs 29 | 29 vs 10 | 49% thal exp | 0.28 (0.19-0.41) | 0.45 (0.25-0.80) | 16.7 vs 7.1 | NG |
| 42% len exp | 0.38 (0.26-0.56) | |||||||||
| 21% to len | 0.36 (0.21-0.63) | |||||||||
| elo/btz/dex vs btz/dex34 | 77 vs 75 | 1 (1-3) | 66 vs 63 | 33 vs 23 | 4 vs 3 | 74% IMID exp | 0.87 (0.56-1.34) | NE | 9.7 vs 6.9 | NG |
| btz/pom/dex35 | 50 | 2 (1-5) | 86 | 50 | 22 | 100% to len | 86% in len ref | 100% in del(17p) | 13.7 | NG |
| benda/btz/dex37 | 75 | 1 (1-4) | 77 | 20 | 20 | 32% to IMID | 84% | 75% | 15.5 | NG |
| benda/len/dex38 | 29 | 3 (1-6) | 52 | 24 | 0 | 52% to IMID | 69% | 60% | 6.1 | NG |
| Refractory to PI | ||||||||||
| btz/len/dex39 | 64 | NG | 64 | 28 | 25 | 53% btz exp | 67% in rel/ref | 50% | 9.5 | 30 |
| 42% rel/ref | ||||||||||
| cfz/len/dex40 | 52 | 3 (1-5) | 77 | 42 | 6 | 25% to btz | 69% in btz ref | NG | 15.4 | NG |
| 44% to len | ||||||||||
| dara/len/dex vs len/dex (POLLUX)41 | 286 vs 283 | 1 (1-11) | 93 vs 76 | 79 vs 48 | 51 vs 21 | 84% btz exp | 0.40 (0.30-0.54) | 0.53 (0.25-1.13) | NR vs 17.5 | NG |
| 21% to btz | 0.46 (0.26-0.80) | |||||||||
| elo/len/dex vs len/dex (ELOQUENT-2)42,43 | 321 vs 325 | 2 (1-4) | 79 vs 66 | 28 vs 21 | 4 vs 7 | 70% btz exp | 0.66 (0.53-0.83) | 0.65 (0.45-0.94) in del(17p) | 19.4 vs 14.9 | 48 vs 40 |
| cfz (56 mg/m2)44 | 24 | 5 (2-9) | 50 | 21 | 4 | 75% to btz | NG | NG | 6.2 | NG |
| 83% to len |
| Intervention (study name) . | N . | Prior lines or regimens, median (range), n . | ORR (%) . | VGPR or better (%) . | CR or better (%) . | Refractory population* . | PFS HR (95% CI) † or RR in refractory population . | PFS HR† or RR in high risk‡ . | Median PFS (mo) . | Median OS (mo) . |
|---|---|---|---|---|---|---|---|---|---|---|
| Refractory to IMID | ||||||||||
| ixa/len/dex vs pbo/len/dex (TOURMALINE-MM1)26,27 | 360 vs 362 | 1 (1-3) | 78 vs 72 | 48 vs 39 | 12 vs 7 | 55% IMID exp | 0.74 (0.54-1.03) in IMID exp | 0.54 (0.32-0.92) | 20.6 vs 14.7 | NG |
| 12% to thal | 0.73 (0.37-1.44) in thal ref | |||||||||
| ixa/dex28 | 35 | 4 (2-8) | 31 | 23 | 3 | 46% to len | 31% | 20% | 8.4 | NG |
| cfz/dex vs btz/dex (ENDEAVOR)30 | 464 vs 465 | 2 (1-2) | 77 vs 63 | 54 vs 29 | 13 vs 6 | 25% to len | 0.80 (0.57-1.11) | 0.65 (0.45-0.92) | 18.7 vs 9.4 | 47.6 vs 40.0 |
| cfz/len/dex vs len/dex (ASPIRE)31,32 | 396 vs 396 | 2 (1-3) | 87 vs 67 | 70 vs 40 | 32 vs 9 | 22% to IMID | 0.64 (0.44-0.91) | 0.70 (0.43-1.16) | 26.3 vs 17.6 | 48.3 vs 40.4 |
| dara/btz/dex vs btz/dex (CASTOR)33 | 251 vs 247 | 2 (1-10) | 84 vs 63 | 62 vs 29 | 29 vs 10 | 49% thal exp | 0.28 (0.19-0.41) | 0.45 (0.25-0.80) | 16.7 vs 7.1 | NG |
| 42% len exp | 0.38 (0.26-0.56) | |||||||||
| 21% to len | 0.36 (0.21-0.63) | |||||||||
| elo/btz/dex vs btz/dex34 | 77 vs 75 | 1 (1-3) | 66 vs 63 | 33 vs 23 | 4 vs 3 | 74% IMID exp | 0.87 (0.56-1.34) | NE | 9.7 vs 6.9 | NG |
| btz/pom/dex35 | 50 | 2 (1-5) | 86 | 50 | 22 | 100% to len | 86% in len ref | 100% in del(17p) | 13.7 | NG |
| benda/btz/dex37 | 75 | 1 (1-4) | 77 | 20 | 20 | 32% to IMID | 84% | 75% | 15.5 | NG |
| benda/len/dex38 | 29 | 3 (1-6) | 52 | 24 | 0 | 52% to IMID | 69% | 60% | 6.1 | NG |
| Refractory to PI | ||||||||||
| btz/len/dex39 | 64 | NG | 64 | 28 | 25 | 53% btz exp | 67% in rel/ref | 50% | 9.5 | 30 |
| 42% rel/ref | ||||||||||
| cfz/len/dex40 | 52 | 3 (1-5) | 77 | 42 | 6 | 25% to btz | 69% in btz ref | NG | 15.4 | NG |
| 44% to len | ||||||||||
| dara/len/dex vs len/dex (POLLUX)41 | 286 vs 283 | 1 (1-11) | 93 vs 76 | 79 vs 48 | 51 vs 21 | 84% btz exp | 0.40 (0.30-0.54) | 0.53 (0.25-1.13) | NR vs 17.5 | NG |
| 21% to btz | 0.46 (0.26-0.80) | |||||||||
| elo/len/dex vs len/dex (ELOQUENT-2)42,43 | 321 vs 325 | 2 (1-4) | 79 vs 66 | 28 vs 21 | 4 vs 7 | 70% btz exp | 0.66 (0.53-0.83) | 0.65 (0.45-0.94) in del(17p) | 19.4 vs 14.9 | 48 vs 40 |
| cfz (56 mg/m2)44 | 24 | 5 (2-9) | 50 | 21 | 4 | 75% to btz | NG | NG | 6.2 | NG |
| 83% to len |
benda, bendamustine; CI, confidence interval; elo, elotuzumab; exp, exposed; ixa, ixazomib; NE, nonestimable; NG, not given; NR, not reached; ORR, overall response rate; pbo, placebo; pom, pomalidomide; rel/ref, relapsed and refractory; 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.