A phase II Bayesian sequential clinical trial in advanced Waldenström macroglobulinemia patients treated with bortezomib: interest of addition of dexamethasone

Leuk Lymphoma. 2017 Nov;58(11):2615-2623. doi: 10.1080/10428194.2017.1307357. Epub 2017 Apr 10.

Abstract

In patients with advanced Waldenström macroglobulinemia (WM), overall response rate (ORR) and median progression-free survival (PFS) achieved with bortezomib alone and bortezomib rituximab combination were 27-85% and 7.9 months, and 81% and 16.4 months, respectively. We checked the role of dexamethasone in combination with bortezomib by enrolling in a phase II trial 34 patients with relapsed/refractory WM. Bortezomib (1.3 mg/m2 IV D1, 4, 8, and 11 every 21 days) was used for six cycles. In non-responding patients, dexamethasone (20 mg daily for two days) was added to each infusion after the second cycle. After two cycles, the Bayes estimated ORR was 43.2 (95% Credible Interval: 28.0-59.1%) using the informative prior. Two-year survival rate was 84.0% and the median PFS 15.3 months without difference between patients treated with or without dexamethasone. We conclude that dexamethasone must be associated to bortezomib-based regimen.

Keywords: Bayes; Dexamethasone; Waldenström macroglobulinemia; bortezomib.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bayes Theorem*
  • Bortezomib / administration & dosage
  • Bortezomib / adverse effects
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects
  • Female
  • Hematologic Diseases / chemically induced
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Prospective Studies
  • Remission Induction
  • Waldenstrom Macroglobulinemia / drug therapy*
  • Waldenstrom Macroglobulinemia / pathology

Substances

  • Bortezomib
  • Dexamethasone