Selected therapy regimens in AL amyloidosis
| Therapy regimens . | Dosing schedule . | N (F) . | H (stage III) . | HR/CR (OR) . | Most common grade ≥3 SAE . | 100-d mortality . | Median PFS/OS (y) . |
|---|---|---|---|---|---|---|---|
| Controlled phase 3 trial | |||||||
| MDex | M 10 mg/m2 + Dex 40 mg days 1-4 q28 | 43 (100%) | 46% | 68%/32% (39%) | Overall 16% | 2% | TTP 2.7/OS 4.7 |
| vs ASCT42 | M 140-200 mg/m2 | 37 (100%) | 48% | 67%/41% (45%) | Hemodialysis 22% | 24% | TTP 2.7/OS 1.8 |
| Autologous stem cell transplantation | |||||||
| ASCT45 | M 100-200 mg/m2 | 421 (76%) | 45% | M200 -/43% | — | M200 9% | M200 3.4/8.4 |
| M100-140 -/24% (53%) | M100-140 14% | M100-140 1.8/3.8 | |||||
| ASCT41 | M 100-200 mg/m2 | 434 | 49% (25%) | 76%/39% (47%) | — | 10% | CR -/not reached |
| PR -/8.9 | |||||||
| NR -/2.7 | |||||||
| Risk-adapted ASCT48 | M 100/140/200 mg/m2 | 40 (100%) | 65% (28%) | 79%/58% (70%) | During BDex, Tp 43%, cardiac 20%, anemia 13% | ASCT 10% | At 2 y: 69%/82% |
| B 1.3 mg/m2 (OW first 2 cycles, then TW) | BDex 4% | ||||||
| Dex 20 mg day of B and following day | |||||||
| Conventional chemotherapy | |||||||
| MDex55,56 | M 0.22 mg/kg + Dex 40 mg days 1-4 q28 | 46 (100%) | 70% | 67%/33% (48%) | Overall 11%, infection 6% | 4% | 3.8/5.1 |
| Immune-modulatory–based therapy | |||||||
| CTD57 | C 500 mg on days 1, 8, 15 q21/28 | 75 (41%) | 59% | 74%/21% (27%) | Grade ≥2: sedation 40%, fluid retention 21% | 4% | 1.7/3.4 |
| T 50-200 mg/d | |||||||
| Dex 40 mg on days 1-4, 9-12 q21 | |||||||
| or 20 mg on days 1-4 and 15-18q28 | |||||||
| LDex61 | L up to 25 mg on days 1-21 q28 | 22 (41%) | 64% (23%) | 41%/- (23%) | Overall 86%, neutropenia 45%, Tp 27%, rash 18%, infection 18%, fatigue 18% | 18% | 1.6/- |
| Dex 40 mg on days 1-4, 15-18 q28 | |||||||
| added in nonresponders to L alone | |||||||
| CLD66 | C 300 mg/m2 on days 1, 8, 15 q 28 | 35 (11%) | 63% (43%) | 60%/11% (31%) | Overall 74%, Np 40%, Tp 40%, rash 10%, thrombosis 10% | 9% | 2.4/3.1 |
| L 15 mg on days 1-21 q 28 | |||||||
| Dex 40 mg on days 1, 8, 15, 22 q28 | |||||||
| MLD69 | M 0.18 mg/kg on days 1-4 q28 | 26 (100%) | 58% | 58%/23%, 42% with full-dose L (50%) | Overall 81%, Np 11%, heart failure 11% | — | At 2 y: 54%/81% |
| L 5-15 mg on days 1-21 q28 | |||||||
| Dex 40 mg on days 1-4 q28 | |||||||
| PDex63 | Pomalidomide 2 mg/d | 33 (0) | 82% (25%) | 48%/3% (15%) | Np 30%, infection 27%, arrhythmia 21%, fatigue 18% | 3% | 1.2/2.3 |
| Dex 40 mg OW | |||||||
| Proteasome inhibitor–based therapy | |||||||
| Bortezomib60 | 1.6 mg/m2 OW | 70 (0) | 56% | OW: 69%/38% | Overall OW 50%, TW 79% | 3% | At 1 y: OW: 72%/93% |
| 1.3 mg/m2 TW | TW: 67%/24% (29%) | Tp 18% (TW), vomiting 12% (TW) | TW: 75%/84% | ||||
| CyBorD50 | C 350 mg/m2 on days 1, 8, 15 B 1.0-1.3 mg/m2 TW | 43 (47%) | 74% (46%) | 81%/65% frontline, 22% pretreated (46%) | 19% discontinued (due to neuropathy in 14%) | 0 | At 2 y: 53%/98% |
| Dex 20 mg TW | |||||||
| Ixazomib71 | 4.0 mg on days 1, 8, 15 q28 (MTD) | 16 (0) | 69% (6%) | 42%/8%, | (Any grade) nausea 31%, diarrhea 25%, thrombocytopenia 25% | 0 | — |
| Dex 40 mg on days 1-4 (added in nonresponders) | VGPR 25% (-) |
| Therapy regimens . | Dosing schedule . | N (F) . | H (stage III) . | HR/CR (OR) . | Most common grade ≥3 SAE . | 100-d mortality . | Median PFS/OS (y) . |
|---|---|---|---|---|---|---|---|
| Controlled phase 3 trial | |||||||
| MDex | M 10 mg/m2 + Dex 40 mg days 1-4 q28 | 43 (100%) | 46% | 68%/32% (39%) | Overall 16% | 2% | TTP 2.7/OS 4.7 |
| vs ASCT42 | M 140-200 mg/m2 | 37 (100%) | 48% | 67%/41% (45%) | Hemodialysis 22% | 24% | TTP 2.7/OS 1.8 |
| Autologous stem cell transplantation | |||||||
| ASCT45 | M 100-200 mg/m2 | 421 (76%) | 45% | M200 -/43% | — | M200 9% | M200 3.4/8.4 |
| M100-140 -/24% (53%) | M100-140 14% | M100-140 1.8/3.8 | |||||
| ASCT41 | M 100-200 mg/m2 | 434 | 49% (25%) | 76%/39% (47%) | — | 10% | CR -/not reached |
| PR -/8.9 | |||||||
| NR -/2.7 | |||||||
| Risk-adapted ASCT48 | M 100/140/200 mg/m2 | 40 (100%) | 65% (28%) | 79%/58% (70%) | During BDex, Tp 43%, cardiac 20%, anemia 13% | ASCT 10% | At 2 y: 69%/82% |
| B 1.3 mg/m2 (OW first 2 cycles, then TW) | BDex 4% | ||||||
| Dex 20 mg day of B and following day | |||||||
| Conventional chemotherapy | |||||||
| MDex55,56 | M 0.22 mg/kg + Dex 40 mg days 1-4 q28 | 46 (100%) | 70% | 67%/33% (48%) | Overall 11%, infection 6% | 4% | 3.8/5.1 |
| Immune-modulatory–based therapy | |||||||
| CTD57 | C 500 mg on days 1, 8, 15 q21/28 | 75 (41%) | 59% | 74%/21% (27%) | Grade ≥2: sedation 40%, fluid retention 21% | 4% | 1.7/3.4 |
| T 50-200 mg/d | |||||||
| Dex 40 mg on days 1-4, 9-12 q21 | |||||||
| or 20 mg on days 1-4 and 15-18q28 | |||||||
| LDex61 | L up to 25 mg on days 1-21 q28 | 22 (41%) | 64% (23%) | 41%/- (23%) | Overall 86%, neutropenia 45%, Tp 27%, rash 18%, infection 18%, fatigue 18% | 18% | 1.6/- |
| Dex 40 mg on days 1-4, 15-18 q28 | |||||||
| added in nonresponders to L alone | |||||||
| CLD66 | C 300 mg/m2 on days 1, 8, 15 q 28 | 35 (11%) | 63% (43%) | 60%/11% (31%) | Overall 74%, Np 40%, Tp 40%, rash 10%, thrombosis 10% | 9% | 2.4/3.1 |
| L 15 mg on days 1-21 q 28 | |||||||
| Dex 40 mg on days 1, 8, 15, 22 q28 | |||||||
| MLD69 | M 0.18 mg/kg on days 1-4 q28 | 26 (100%) | 58% | 58%/23%, 42% with full-dose L (50%) | Overall 81%, Np 11%, heart failure 11% | — | At 2 y: 54%/81% |
| L 5-15 mg on days 1-21 q28 | |||||||
| Dex 40 mg on days 1-4 q28 | |||||||
| PDex63 | Pomalidomide 2 mg/d | 33 (0) | 82% (25%) | 48%/3% (15%) | Np 30%, infection 27%, arrhythmia 21%, fatigue 18% | 3% | 1.2/2.3 |
| Dex 40 mg OW | |||||||
| Proteasome inhibitor–based therapy | |||||||
| Bortezomib60 | 1.6 mg/m2 OW | 70 (0) | 56% | OW: 69%/38% | Overall OW 50%, TW 79% | 3% | At 1 y: OW: 72%/93% |
| 1.3 mg/m2 TW | TW: 67%/24% (29%) | Tp 18% (TW), vomiting 12% (TW) | TW: 75%/84% | ||||
| CyBorD50 | C 350 mg/m2 on days 1, 8, 15 B 1.0-1.3 mg/m2 TW | 43 (47%) | 74% (46%) | 81%/65% frontline, 22% pretreated (46%) | 19% discontinued (due to neuropathy in 14%) | 0 | At 2 y: 53%/98% |
| Dex 20 mg TW | |||||||
| Ixazomib71 | 4.0 mg on days 1, 8, 15 q28 (MTD) | 16 (0) | 69% (6%) | 42%/8%, | (Any grade) nausea 31%, diarrhea 25%, thrombocytopenia 25% | 0 | — |
| Dex 40 mg on days 1-4 (added in nonresponders) | VGPR 25% (-) |
B, bortezomib; BDex, bortezomib dexamethasone; C, cyclophosphamide; CLD, cyclophosphamide, lenalidomide, dexamethasone; Dex, dexamethasone; F, frontline therapy; H, heart involvement; HR, overall hematologic response; L, lenalidomide; LDex, lenalidomide plus dexamethasone; M, melphalan; MLD, melphalan, lenalidomide, dexamethasone; MTD, maximum tolerated dose; N, number of patients; Np, neutropenia; NR, nonresponders; OR, organ response; OS, overall survival; OW, once weekly; PDex, pomalidomide plus dexamethasone; PFS, progression-free survival; PR, partial response; q, every; SAE, severe adverse events; T, thalidomide; Tp, thrombocytopenia; TTP, time to hematologic progression; TW, twice weekly.
Intention-to-treat response rates are reported.