NOTCH1 activating mutations (~10-15% of CLL) — adverse prognostic; reduced response to an...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-NOTCH1-ACTIVATING-CLL |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-CLL |
| Sources | SRC-CIVIC SRC-ESMO-CLL-2024 SRC-NCCN-BCELL-2025 |
Actionability Facts
| Biomarker | BIO-NOTCH1-MUTATION |
|---|---|
| Variant | activating (PEST domain truncating, c.7541_7542delCT canonical) |
| Disease | DIS-CLL |
| ESCAT tier | IIIA |
| Recommended combinations | venetoclax + obinutuzumab (CLL14), acalabrutinib monotherapy, zanubrutinib monotherapy |
| Contraindicated monotherapy | chlorambucil + obinutuzumab (relatively reduced anti-CD20 benefit per NOTCH1-mut subgroup) |
| Evidence summary | NOTCH1 activating mutations (~10-15% of CLL) — adverse prognostic; reduced response to anti-CD20 mAb (rituximab, obinutuzumab) in some studies. Venetoclax-based fixed-duration (CLL14) and BTKi continuous remain effective. Not directly targeted; selects venetoclax-based therapy when present. |
Notes
ESCAT IIIA. NOTCH1 mutation identifies a subgroup that may be especially well-served by venetoclax-based regimens vs anti-CD20-based chemoimmuno.
Used By
No reverse references found in the YAML corpus.