Phase 2 trial of bortezomib in combination with rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with bortezomib, rituximab, methotrexate, and cytarabine for untreated mantle cell lymphoma

Cancer. 2018 Jun 15;124(12):2561-2569. doi: 10.1002/cncr.31361. Epub 2018 May 3.

Abstract

Background: Although the outcomes of patients with mantle cell lymphoma (MCL) have improved, there is still no cure. Bortezomib has a 33% response rate in relapsed/refractory MCL and has shown additive and/or synergistic effects in preclinical trials with known effective agents.

Methods: This is a report of a prospective phase 2 trial of bortezomib added to rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (BzR-hyperCVAD)/rituximab, high-dose methotrexate, and high-dose cytarabine (BzR-MA) for 95 patients with newly diagnosed MCL.

Results: The overall and complete response rates were 100% and 82%, respectively. Hematologic toxicity was high but expected and did not lead to an increased incidence of neutropenic fever or dose reductions in comparison with a similar reported regimen without bortezomib. After a median follow-up of 44 months, the median overall survival had not been reached, and the time to treatment failure (TTF) was 55 months, which is not different from that of historical controls.

Conclusions: BzR-hyperCVAD/BzR-MA at the dose and schedule studied produced high rates of response and a TTF similar to that of historical reports without bortezomib. Cancer 2018;124:2561-9. © 2018 American Cancer Society.

Keywords: and dexamethasone (R-hyperCVAD); bortezomib; doxorubicin; mantle cell lymphoma; rituximab plus hyperfractionated cyclophosphamide; vincristine.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bortezomib / administration & dosage
  • Bortezomib / adverse effects
  • Chemotherapy-Induced Febrile Neutropenia / epidemiology*
  • Chemotherapy-Induced Febrile Neutropenia / etiology
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Cytarabine / administration & dosage
  • Cytarabine / adverse effects
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Kaplan-Meier Estimate
  • Lymphoma, Mantle-Cell / drug therapy*
  • Lymphoma, Mantle-Cell / mortality
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / prevention & control
  • Prospective Studies
  • Rituximab / administration & dosage
  • Rituximab / adverse effects
  • Survival Rate
  • Time Factors
  • Treatment Failure
  • Vincristine / administration & dosage
  • Vincristine / adverse effects

Substances

  • Cytarabine
  • Rituximab
  • Vincristine
  • Bortezomib
  • Dexamethasone
  • Doxorubicin
  • Cyclophosphamide
  • Methotrexate