Outcomes of patients with relapsed/refractory lymphoplasmacytic lymphoma/Waldenström macroglobulinemia treated with venetoclax: a multicenter retrospective analysis
Venetoclax demonstrated a high overall response rate (~70%) and a prolonged progression‑free survival (median 28.5 months, 2‑year PFS 57%) in heavily pretreated patients with relapsed/refractory lymphoplasmacytic lymphoma/Waldenström macroglobulinemia.
Venetoclax showed promising activity in a small phase II trial in relapsed/refractory Waldenström macroglobulinemia (WM). To report the clinical activity of venetoclax and prognostic factors associated with outcomes in a larger cohort, we retrospectively identified 76 patients with relapsed/refractory lymphoplasmacytic lymphoma (LPL/WM) treated with venetoclax monotherapy at nine US medical centers. The median age at venetoclax treatment initiation was 66 years. MYD88, CXCR4, and TP53 mutations were detected in 65 (94 %), 23 (40 %), and 10 (22 %) patients, respectively. The median number of prior lines of treatment was 3, including covalent BTK inhibitor in 82 % and alkylating agent in 71 % of patients. The overall and major response rates to venetoclax were 70 % and 63 %, respectively. The median and 2‑year progression‑free survival (PFS) were 28.5 months and 57 %, respectively. The median and 2‑year overall survival were not reached and 82 %, respectively. Prior treatment with BTK inhibitor was the only factor associated with PFS in multivariate analysis (hazard ratio 2.97, p = 0.012). Venetoclax dose interruptions and/or reductions occurred in 27 patients (41 %). Five patients (7 %) developed laboratory tumor lysis syndrome (TLS), including 3 (4 %) with clinical TLS. Venetoclax resulted in a high response rate and a prolonged PFS in patients with heavily pretreated LPL/WM.
Lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) is an uncommon indolent B‑cell non‑Hodgkin lymphoma characterized by recurrent relapses and progressively shortening responses or resistance to subsequent treatments. Most patients respond to conventional chemoimmunotherapy, proteasome inhibitors, or Bruton tyrosine kinase inhibitors (BTKi), yet relapses are inevitable and more active therapies for relapsed or refractory disease are needed.
Bizonyítékszint: Klinikai vizsgálat. Formális klinikai vizsgálati eredmény.
Kapcsolódó jelek
- Waldenström Macroglobulinemia Clinical Trials
- European Consortium for Waldenström's Macroglobulinemia
- Waldenström Macroglobulinemia - A State-of-the-Art Review: Part 2- Focus on Therapy
- The therapeutic perspective of relapsed/refractory Waldenström Macroglobulinemia: what comes next?
- Phase 3 Trial of Ibrutinib plus Rituximab in Waldenström's Macroglobulinemia