Primary therapy of Waldenström macroglobulinemia with bortezomib, dexamethasone, and rituximab: WMCTG clinical trial 05-180

J Clin Oncol. 2009 Aug 10;27(23):3830-5. doi: 10.1200/JCO.2008.20.4677. Epub 2009 Jun 8.

Abstract

Purpose: We examined the activity of bortezomib, dexamethasone, and rituximab (BDR) in patients with symptomatic, untreated Waldenström macroglobulinemia (WM).

Patients and methods: A cycle of therapy consisted of bortezomib 1.3 mg/m(2) intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11; and rituximab 375 mg/m(2) on day 11. Patients received four consecutive cycles for induction therapy and then four more cycles, each given 3 months apart, for maintenance therapy. Twenty-three patients received a median of seven cycles of treatment.

Results: Median bone marrow disease involvement declined from 55% to 10% (P = .0004), serum immunoglobulin M levels declined from 4,830 to 1,115 mg/dL (P < .0001), and hematocrit increased from 29.8% to 38.2% (P = .0002) at best response. The overall response rates and major response rates were 96% and 83% with three complete responses, two near complete responses, three very good partial responses, 11 partial responses, and three minor responses. Responses occurred at a median of 1.4 months. With a median follow-up of 22.8 months, 18 of 23 patients remained free of disease progression. Peripheral neuropathy was the most common toxicity, and it resolved to grade < or = 1 in 13 of 16 patients at a median of 6.0 months. Four of the first seven treated patients developed herpes zoster, resulting in the institution of prophylactic antiviral therapy.

Conclusion: The results demonstrate that BDR produces rapid and durable responses, along with high rates of response and complete remissions in WM. Herpes zoster prophylaxis is necessary with BDR, and reversible peripheral neuropathy was the most common toxicity leading to premature discontinuation of bortezomib in 61% of patients. Exploration of alternative schedules for bortezomib administration that includes weekly dosing should be pursued.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Blood Viscosity / drug effects
  • Bone Marrow Neoplasms / drug therapy
  • Bone Marrow Neoplasms / secondary
  • Boronic Acids / administration & dosage
  • Boronic Acids / adverse effects
  • Bortezomib
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Hematocrit
  • Herpes Zoster / chemically induced
  • Herpes Zoster / prevention & control
  • Humans
  • Immunoglobulin M / blood
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Platelet Count
  • Pyrazines / administration & dosage
  • Pyrazines / adverse effects
  • Rituximab
  • Treatment Outcome
  • Waldenstrom Macroglobulinemia / blood
  • Waldenstrom Macroglobulinemia / drug therapy*
  • Waldenstrom Macroglobulinemia / pathology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Boronic Acids
  • Immunoglobulin M
  • Pyrazines
  • Rituximab
  • Bortezomib
  • Dexamethasone