MAPK-targeted therapies in patients with LCH and other histiocytic disorders
| Disease . | Drug name (target) . | Dose . | N . | Age, y . | Pathogenic variants . | Disease characteristics . | Response . | Response after DC . | Reference . |
|---|---|---|---|---|---|---|---|---|---|
| LCH | Vemurafenib* (BRAF) | 8.5-33.8 mg/kg/d | 1 | 0.7 | BRAF-V600E | RR-MS | CR 1/1 | Relapse 1/1 | 29 |
| LCH | Vemurafenib* (BRAF) | 20 mg/kg/d | 54 | 0.2-14 | BRAF-V600E | RR-MS | CR 38/54 PR 16/54 | Relapse 14/30 | 30 |
| LCH | Dabrafenib* (BRAF) Vemurafenib* (BRAF) Trametinib* (BRAF) | NA | 21 | 0.4-21 | BRAF-V600E | RR-MS CNS-ND (13) | CR 4/21 PR 14/21 SD 2/21 PD 1/21 | NA | 13 |
| LCH | Dabrafenib* (BRAF) Trametinib* (BRAF) | D: 5 mg/kg/d T: NA | 4 | 0.1-36 | BRAF-V600E BRAF indel | RR-MS CNS-ND (1) | CR 3/4 PR 1/4 | NA | 34 |
| LCH | Dabrafenib* (BRAF) | 4 mg/kg/d | 20 | 0.6-6 | BRAF-V600E | RR-MS | CR 0/20 PR 14/20 SD 2/20 PD 4/20 | NA | 32 |
| LCH | Dabrafenib* (BRAF) Trametinib* (BRAF) | D: 4.5-5.25 mg/kg/d T: 0.025-0.032 mg/kg/d | 25 D: 13 D+T: 12 | 1-13 | BRAF-V600E | RR-MS (24) CNS-ND (1) | ORR: D: 76.9% D+T: 58.3% | NA | 33 |
| ECD, LCH | Vemurafenib† (BRAF) | 960 mg bid | 26 | 51-74 | BRAF-V600E | Refractory (17/26) CNS (11/26) | CR 2/26 PR 14/26 SD 9/26 | NA | 31 |
| ECD, LCH, RDD, mixed | Cobimetinib‡ (MEK) | 60 mg daily | 18 | 18-80 | BRAF-V600E BRAF MEK1 ARAF MEK2 NRAS WT BRAF | Refractory and/or multisystem and/or brain and/or cardiac involvement | CR 13/18 PR 3/18 SD 1/18 ND 1/18 | NA | 35 |
| Disease . | Drug name (target) . | Dose . | N . | Age, y . | Pathogenic variants . | Disease characteristics . | Response . | Response after DC . | Reference . |
|---|---|---|---|---|---|---|---|---|---|
| LCH | Vemurafenib* (BRAF) | 8.5-33.8 mg/kg/d | 1 | 0.7 | BRAF-V600E | RR-MS | CR 1/1 | Relapse 1/1 | 29 |
| LCH | Vemurafenib* (BRAF) | 20 mg/kg/d | 54 | 0.2-14 | BRAF-V600E | RR-MS | CR 38/54 PR 16/54 | Relapse 14/30 | 30 |
| LCH | Dabrafenib* (BRAF) Vemurafenib* (BRAF) Trametinib* (BRAF) | NA | 21 | 0.4-21 | BRAF-V600E | RR-MS CNS-ND (13) | CR 4/21 PR 14/21 SD 2/21 PD 1/21 | NA | 13 |
| LCH | Dabrafenib* (BRAF) Trametinib* (BRAF) | D: 5 mg/kg/d T: NA | 4 | 0.1-36 | BRAF-V600E BRAF indel | RR-MS CNS-ND (1) | CR 3/4 PR 1/4 | NA | 34 |
| LCH | Dabrafenib* (BRAF) | 4 mg/kg/d | 20 | 0.6-6 | BRAF-V600E | RR-MS | CR 0/20 PR 14/20 SD 2/20 PD 4/20 | NA | 32 |
| LCH | Dabrafenib* (BRAF) Trametinib* (BRAF) | D: 4.5-5.25 mg/kg/d T: 0.025-0.032 mg/kg/d | 25 D: 13 D+T: 12 | 1-13 | BRAF-V600E | RR-MS (24) CNS-ND (1) | ORR: D: 76.9% D+T: 58.3% | NA | 33 |
| ECD, LCH | Vemurafenib† (BRAF) | 960 mg bid | 26 | 51-74 | BRAF-V600E | Refractory (17/26) CNS (11/26) | CR 2/26 PR 14/26 SD 9/26 | NA | 31 |
| ECD, LCH, RDD, mixed | Cobimetinib‡ (MEK) | 60 mg daily | 18 | 18-80 | BRAF-V600E BRAF MEK1 ARAF MEK2 NRAS WT BRAF | Refractory and/or multisystem and/or brain and/or cardiac involvement | CR 13/18 PR 3/18 SD 1/18 ND 1/18 | NA | 35 |
D, dabrafenib; NA, not available; ND, neurodegeneration; PD, progressive disease; PR, partial response; RDD, Rosai-Dorfman disease; SD, stable disease; T, trametinib; WT, wild-type.
Drug is not FDA approved for this indication.
Drug is FDA approved for ECD with BRAF-V600E mutation.
Drug is FDA approved for adults with histiocytic neoplasms.