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.

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.

• Authors: Jorge E Romaguera, Michael Wang, Lei Feng, Luis E Fayad, Frederick Hagemeister, Peter McLaughlin, M Alma Rodriguez, Michelle Fanale, Robert Orlowski, Larry W Kwak, Sattva Neelapu, Yasuhiro Oki, Barbara Pro, Anas Younes, Felipe Samaniego, Nathan Fowler, Kimberly Hartig, Marisa Valentinetti, Judy Smith, Peggy Ford, Adam Naig, L Jeffrey Medeiros, Hagop M Kantarjian, Andre Goy
• Journal: Cancer (Cancer) Vol. 124 Issue 12 Pg. 2561-2569 (06 15 2018) ISSN: 1097-0142 [Electronic] United States
• PMID: 29723393 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 American Cancer Society.

Chemical References

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

Topics

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