TABLE 3:
Results of Randomized KarMMa-3 and CARTITUDE-4 trials of Early Line CAR T
| KarMMa-3 [7] | CARTITUDE-4 [6, 83] | |||
|---|---|---|---|---|
| Ide-Cel | SOC | Cilta-Cel | SOC | |
| Study Design | ||||
| Inclusion Criteria | 2-4 prior lines including PI + IMiD + Dara | 1-3 prior lines, Len refractory | ||
| Lymphodepleting Chemo | Flu 30 mg/m2 + Cy 300 mg/m2 x3d | Flu 30 mg/m2 + Cy 300 mg/m2 x3d | ||
| Therapy given | CAR T | Choice: DPd, DVd, IRd, Kd, or EPd | CAR T | Choice: DPd or PVd |
| CAR T-Cell Dose, median (range) | 445x106 (175-529x106) | N/A | 0.71x106/kg | N/A |
| Baseline Characteristics | ||||
| No of pts Randomized | 254 | 132 | 208 | 211 |
| Completed Apheresis (%) | 249 (98) | N/A | 208 | N/A |
| Manufacturing Failure (%) | 3 (1) | N/A | 0 (0) | N/A |
| No Infused/Treated (%) | 225 (89) | 126 (95) | 176 (85) | 208 (99) |
| Median time from apheresis to infusion, days (range) | 49 (34-117) | N/A | 44 (25-127) | N/A |
| Median Age (range) years | 63 (30-81) | 63 (42-83) | 61.5 (27-78) | 61 (35-80) |
| Age ≥ 65 (%) | 104 (41) | 54 (41) | NR | NR |
| Age ≥ 75 (%) | 12 (5) | 9 (7) | NR | NR |
| Male sex (%) | 156 (61) | 79 (60) | 116 (56) | 124 (59) |
| White race (%) | 172 (68) | 78 (59) | 157 (76) | 157 (75) |
| Black race (%) | 18 (7) | 18 (14) | 6 (3) | 7 (3) |
| R-ISS II (%) | 150 (59) | 82 (62) | 60 (29) | 65 (31) |
| R-ISS III (%) | 31 (12) | 14 (11) | 12 (6) | 14 (7) |
| ECOG 0-1 (%) | 153 (99) | 128 (97) | 207 (99.5) | 210 (99.5) |
| High risk FISH (non-1q) (%) | 107 (42) | 61 (46) | 73/207 (35) | 69/210 (33) |
| Add 1q (gain or amp) (%) | 125 (49) | 51 (39) | 89/207 (43) | 107/210 (63) |
| Extramedullary Disease (%) | 61 (24) | 32 (24) | 44 (21) | 35 (17) |
| High Tumor Burden (%) | 71 (28) | 34 (26) | 42/206 (20) | 43/208 (21) |
| Median Prior Lines (range) | 3 (2-4) | 3 (2-4) | 2 (1-3) | 2 (1-3) |
| Refractory to anti-CD38 Ab | 242 (95) | 123 (93) | 50 (24) | 46 (22) |
| Triple Class Refractory (%) | 164 (65) | 89 (67) | 30 (14) | 33 (16) |
| Penta-Refractory (%) | 15 (6) | 5 (4) | 2 (1) | 1 (0.5) |
| Efficacy (intent-to-treat) | ||||
| ORR (%) | 181 (71) | 55 (42) | 176 (85) | 142 (67) |
| ≥ CR (%) | 98 (39) | 7 (5) | 152 (73) | 46 (22) |
| ≥ VGPR (%) | 153 (60) | 20 (16) | 169 (81) | 96 (46) |
| MRD Negative 10−5 (%) | 51/254 (20) | 1 (1) | 126/144 (88) | 33/101 (33) |
| ORR for infused pts (%) | NR | NR | 175/176 (99.4) | N/A |
| Progressive Disease as best response (%) | 24 (9) | 10 (8) | 17 (8) | 6 (3) |
| Median DOR, months | 14.8 | 9.7 | Not Reached; 85% at 12 mo | Not Reached; 63% at 12 mo |
| Median PFS, months | 13.3 | 4.4 | Not Reached; 76% at 12 mo | 11.8 49% at 12 mo |
| Median OS, months | Not reached | Not reached | Not Reached, 84% at 12 mo | Not Reached, 84% at 12 mo |
| Safety (for treated pts only) | N=225 | N=126 | N=176 | N=176 |
| Infections Any Grade | 146 (58) | 68 (54) | 129/208 (62) | 148/208 (71) |
| Infections Grade 3-5 | 72 (28) | 26 (20) | 56/208 (27) | 51/208 (25) |
| CRS any grade (%) | 197 (88) | N/A | 134/176 (76) | N/A |
| CRS grade ≥ 3 (%) | 11 (5) | N/A | 2 (1) | N/A |
| Median days to CRS (range) | 1 (1-14) | N/A | 8 (1-23) | N/A |
| Neurotoxicity any grade (%) | 34 (15) | N/A | (4.5) | N/A |
| ICANS grade ≥ 3 (%) | 7 (3) | N/A | 0 (0) | N/A |
| Non-ICANS Neurotoxicity (%) | 0 (0) | N/A | 30 (17%) 1 Parkinsons, 18 CN Palsy, 5 PN | N/A |
Abbreviations: N/A indicates not applicable; NR, not reported; Flu, fludarabine; Cy, cyclophosphamide; DPd, daratumumab, pomalidomide, dexamethasone; DVd, daratumumab + bortezomib + dexamethasone; IRd, ixazomib + lenalidomide + dexamethasone; Kd, carfilzomib + dexamethasone; EPd, elotuzumab + pomalidomide + dexamethasone; PVd, pomalidomide + bortezomib + dexamethasone; CN, cranial nerve; PN, peripheral neuropathy