Venetoclax (BCL2 inhibitor) + azacitidine or decitabine is FDA-approved (Oct 2020) for ne...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-BCL2-EXPRESSION-AML |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-05-03 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-AML |
| Sources | SRC-ELN-AML-2022 SRC-NCCN-AML-2025 SRC-VIALE-A-DINARDO-2020 |
Actionability Facts
| Biomarker | BIO-BCL2-EXPRESSION-IHC |
|---|---|
| Variant | BCL2 protein overexpression by IHC (H-score ≥100 or ≥50% cells 1+/2+/3+) OR BCL2-expressing AML (flow cytometry positivity); note: FDA approval for venetoclax in AML is NOT restricted to BCL2+ patients — overexpression is a predictive enrichment biomarker, not a companion diagnostic |
| Disease | DIS-AML |
| ESCAT tier | IIB |
| Recommended combinations | venetoclax 400 mg/day PO + azacitidine 75 mg/m² SC/IV days 1-7 (28-day cycles; VIALE-A regimen — preferred), venetoclax 400 mg/day PO + decitabine 20 mg/m² IV days 1-5 (28-day cycles; VIALE-C alternative) |
| Contraindicated monotherapy | venetoclax monotherapy in AML (insufficient single-agent activity; HMA backbone required for sustained remissions), venetoclax + azacitidine in CBF-AML (t(8;21) / inv(16)) — inferior to 7+3 + gemtuzumab ozogamicin in fit patients; avoid |
| Evidence summary | Venetoclax (BCL2 inhibitor) + azacitidine or decitabine is FDA-approved (Oct 2020) for newly diagnosed AML in patients ≥75 years or those ineligible for intensive induction chemotherapy, regardless of BCL2 expression status. However, BCL2 protein overexpression and specific co-mutations (IDH1/2, NPM1) are strong predictors of venetoclax response. VIALE-A trial (DiNardo et al. NEJM 2020 — venetoclax + azacitidine vs azacitidine): mOS 14.7 vs 9.6 mo (HR 0.66, p<0.001); CR/CRi rate 66.4% vs 28.3%. BCL2 IHC high-expressors had superior outcomes in retrospective VIALE-A subanalyses. Molecular co-mutation context: NPM1-mutated AML: CR ~75% with ven+aza; IDH2-mutated: CR ~67%; IDH1-mutated: CR ~57%; TP53-mutated: CR ~40% (inferior). AML with t(8;21) or inv(16) (CBF-AML): poor ven response — avoid ven+aza in favor of intensive 7+3 + GO when fit. ESCAT IIB reflects that BCL2 IHC alone is not a mandated companion diagnostic — clinical eligibility criteria (age/fitness) are the primary drivers; BCL2 overexpression adds predictive value in molecular context. |
Notes
ESCAT IIB: BCL2 overexpression is a predictive enrichment marker, not a mandatory companion diagnostic for venetoclax approval in AML. Eligibility is determined by age (≥75) or fitness for intensive chemotherapy. BCL2 IHC or flow cytometry adds predictive information in clinical decision-making, particularly in younger unfit patients where the response probability needs to be weighed. TLS (tumor lysis syndrome) prophylaxis mandatory: ramp-up dosing (20mg → 50mg → 100mg → 200mg → 400mg over 3 days), aggressive hydration, allopurinol/rasburicase. Differentiate from lymphoma indications where BCL2 rearrangement (not just expression) drives ESCAT tier — in AML, BCL2 expression (protein) is the relevant biomarker.
Used By
No reverse references found in the YAML corpus.