CXCR4 WHIM-ähnliche Mutationen co-occur in ~30-40% von MYD88-L265P Waldenström macroglobulinemi...
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| ID | BMA-CXCR4-WHIM-WM |
|---|---|
| Art | Therapeutische Relevanz |
| Status | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Erkrankungen | DIS-WM |
| Quellen | SRC-ESMO-WM-2024 SRC-NCCN-BCELL-2025 |
Fakten zur Handlungsfähigkeit
| Biomarker | BIO-CXCR4-WHIM |
|---|---|
| Variante | CXCR4 WHIM-ähnliche Unsinn/Frameshift-Mutationen (C-terminale Beschneidung, z.B. S338X, R334X); ~30-40% MYD88-L265P Waldenström-Makroglobulinämie |
| Erkrankung | DIS-WM |
| ESCAT-Stufe | IB |
| Empfohlene Kombinationen | bendamustine + rituximab (1L CXCR4-mutated WM per SRC-NCCN-BCELL-2025, SRC-ESMO-WM-2024), bortezomib + dexamethasone + rituximab (BDR, 1L CXCR4-mutated alternative per SRC-NCCN-BCELL-2025), zanubrutinib monotherapy (1L CXCR4-mutated alternative — preserved efficacy vs ibrutinib in CXCR4-mut subgroup of ASPEN trial per SRC-NCCN-BCELL-2025) |
| Kontraindizierte Monotherapie | ibrutinib monotherapy as preferred 1L in CXCR4-mutated WM (slower / less complete response per SRC-ESMO-WM-2024 — alternative; not strict contraindication) |
| Zusammenfassung der Beweise | CXCR4 WHIM-like mutations co-occur in ~30-40% of MYD88-L265P Waldenström macroglobulinemia and confer relative resistance to ibrutinib (BTKi) — lower ORR and major-response rate, slower kinetics of IgM decline (Treon NEJM 2015 — initial cohort; Castillo Blood 2020 — confirmation) per SRC-NCCN-BCELL-2025, SRC-ESMO-WM-2024. CXCR4 status drives 1L therapy selection in WM: in CXCR4-mutated patients, guidelines list bendamustine + rituximab (BR) or proteasome-inhibitor- based regimens (BDR — bortezomib/dex/rituximab) as preferred over BTKi monotherapy; in CXCR4-WT patients, BTKi monotherapy (ibrutinib or zanubrutinib) is preferred. Mavorixafor (CXCR4 antagonist) has FDA orphan designation for WHIM but is investigational in WM. |
Anmerkungen
ESCAT IB / OncoKB Level 3A (predictive of resistance / response modifier rather than a direct drug target). Detection: NGS targeted panel (CXCR4 C-terminal exon 2). Patients with both MYD88-L265P and CXCR4-WHIM mutation have higher disease burden (IgM, BM infiltration) per SRC-NCCN-BCELL-2025. Source-gap: SRC-ASPEN, SRC-INNOVATE-WM not yet ingested.
Verwendet von
Warnhinweis
RF-WM-CXCR4-WHIM-MUTANT- CXCR4 WHIM-ähnlicher Unsinn oder frameshift-Mutation in der C-Terminal-Regulierungsdomäne (z.B....