Journal: Blood advances
This international retrospective study examined 253 treatment‑naïve Waldenström macroglobulinemia patients who received fixed-duration bendamustine‑rituximab and were followed for a median of 5.9 years.
Key findings:
- Efficacy:
- Estimated 5‑year progression‑free survival (PFS): 65%.
- Estimated 5‑year overall survival (OS): 87%.
- MYD88:
- PFS at 5 years was similar in MYD88L265P and MYD88–wild‑type patients (both ~64%).
- This regimen appears equally effective regardless of MYD88 status.
- CXCR4:
- Among 89 patients with known CXCR4 status, 28% had CXCR4 mutations.
- CXCR4‑mutated patients had significantly inferior outcomes:
- Median PFS: 3.3 vs 8.8 years (HR 2.8; P = .0036).
- OS also worse (HR 2.6; P = .036).
- POD24 (progression within 24 months of starting BR):
- Occurred in 11.5% of patients.
- POD24 was associated with:
- Worse subsequent OS (5‑year OS 71% vs 86%; HR 3.1; P = .005).
- Higher mortality versus the general population (standardized mortality ratio [SMR] 3.7).
- In contrast, patients without POD24 had mortality comparable to the general population (SMR 1.1), indicating an excellent long‑term prognosis.
Clinical implications:
- Bendamustine‑rituximab is an effective frontline option for WM independent of MYD88 status.
- CXCR4 mutation identifies a subgroup at higher risk for earlier progression and death.
- POD24 functions as a robust, clinically relevant early surrogate for poor outcome in WM, similar to other indolent lymphomas.
- Patients who avoid POD24 constitute a distinctly favorable‑risk cohort with near‑background mortality.