Phase 2 Open-Label Study of Bortezomib, Cladribine, and Rituximab in Advanced, Newly Diagnosed, and Relapsed/Refractory Mantle-Cell and Indolent Lymphomas

Clin Lymphoma Myeloma Leuk. 2018 Jan;18(1):58-64. doi: 10.1016/j.clml.2017.09.001. Epub 2017 Sep 19.

Abstract

Background: Mantle-cell lymphoma (MCL) and indolent non-Hodgkin lymphoma (iNHL) are incurable heterogeneous diseases characterized by relapse. There is a need for newer treatments in MCL and iNHL, especially in the relapsed/refractory (R/R) setting. We therefore investigated the novel combination of bortezomib (Velcade), cladribine, and rituximab (VCR) in front-line and R/R settings in MCL and iNHL (NCT00980395).

Patients and methods: Eligible patients included adults with biopsy-proven CD20-positive MCL and iNHL who met the criteria for treatment. Rituximab 375 mg/m2 intravenous (IV) day 1, cladribine 4 mg/m2 IV days 1 to 5, and bortezomib 1.3 mg/m2 IV days 1 and 4 were administered every 28 days for 6 cycles.

Results: Twenty-four patients were enrolled onto the study with a median follow-up of 38.5 months. Median age was 66.5 years, and 46% had MCL. The most common adverse events were hematologic, with febrile neutropenia in 3 patients. Neuropathy was noted in 17% of patients, of which 8% was grade 3 or above. The overall response rate was 92%. For the entire cohort, and for MCL patients, the median progression-free survival and the median overall survival were not reached. The 2-year progression-free survival was 82% for the MCL group and 54% for the iNHL group; it was 80% for treatment-naive patients and 57% for R/R patients.

Conclusion: VCR is effective in MCL and iNHL. Although hematologic toxicity can be an issue, this study demonstrates a high response rate to a novel combination and provides an alternative option in transplant-ineligible R/R MCL and iNHL.

Keywords: Clinical trial; Non-Hodgkin's lymphoma; Systemic therapy.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bortezomib / pharmacology
  • Bortezomib / therapeutic use*
  • Cladribine / pharmacology
  • Cladribine / therapeutic use*
  • Female
  • Humans
  • Lymphoma, Mantle-Cell / drug therapy*
  • Lymphoma, Mantle-Cell / pathology
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / pathology
  • Male
  • Neoplasm Recurrence, Local
  • Progression-Free Survival
  • Rituximab / pharmacology
  • Rituximab / therapeutic use*

Substances

  • Cladribine
  • Rituximab
  • Bortezomib

Associated data

  • ClinicalTrials.gov/NCT00980395