First-line treatment with rituximab-hyperCVAD alternating with rituximab-methotrexate-cytarabine and followed by consolidation with 90Y-ibritumomab-tiuxetan in patients with mantle cell lymphoma. Results of a multicenter, phase 2 pilot trial from the GELTAMO group

Haematologica. 2013 Oct;98(10):1563-70. doi: 10.3324/haematol.2013.088377. Epub 2013 Jun 10.

Abstract

The prognosis for fit patients with mantle cell lymphoma has improved with intensive strategies. Currently, the role of maintenance/consolidation approaches is being tested as relapses continue to appear. In this trial we evaluated the feasibility, safety and efficacy of rituximab-hyperCVAD alternating with rituximab-methotrexate-cytarabine followed by consolidation with (90)Y-ibritumomab tiuxetan. Patients received six cycles followed by a single dose of (90)Y-ibritumomab tiuxetan. Thirty patients were enrolled; their median age was 59 years. Twenty-four patients finished the induction treatment, 23 achieved complete remission (77%, 95% confidence interval 60-93) and one patient had progressive disease (3%). Eighteen patients (60%), all in complete remission, received consolidation therapy. In the intent-to-treat population, failure-free, progression-free and overall survival rates at 4 years were 40% (95% confidence interval 20.4-59.6), 52% (95% confidence interval 32.4-71.6) and 81% (95% confidence interval 67.28-94.72), respectively. For patients who received consolidation, failure-free and overall survival rates were 55% (95% confidence interval 31.48-78.52) and 87% (95% confidence interval 70-100), respectively. Hematologic toxicity was significant during induction and responsible for one death (3.3%). After consolidation, grade 3-4 neutropenia and thrombocytopenia were observed in 72% and 83% of patients, with a median duration of 5 and 12 weeks, respectively. Six (20%) patients died, three due to secondary malignancies (myelodysplastic syndrome and bladder and rectum carcinomas). In conclusion, in our experience, rituximab-hyperCVAD alternated with rituximab-methotrexate-cytarabine and followed by consolidation with (90)Y-ibritumomab tiuxetan was efficacious although less feasible than expected. The unacceptable toxicity observed, especially secondary malignancies, advise against the use of this strategy.

Trial registration: clinical.gov identifier: NCT2005-004400-37.

Trial registration: ClinicalTrials.gov NCT00440037 NCT00002005 NCT00440037.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Cytarabine / administration & dosage
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Humans
  • Lymphoma, Mantle-Cell / diagnosis
  • Lymphoma, Mantle-Cell / drug therapy*
  • Lymphoma, Mantle-Cell / epidemiology*
  • Male
  • Methotrexate / administration & dosage
  • Middle Aged
  • Pilot Projects
  • Prospective Studies
  • Rituximab
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Cytarabine
  • Rituximab
  • ibritumomab tiuxetan
  • Methotrexate

Associated data

  • ClinicalTrials.gov/NCT00440037
  • ClinicalTrials.gov/NCT00002005
  • ClinicalTrials.gov/NCT00440037