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.

Abstract

UNLABELLED:

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.

• Authors: Reyes Arranz, Ana García-Noblejas, Carlos Grande, Jimena Cannata-Ortiz, José J Sánchez, José-Antonio García-Marco, Concepción Aláez, Javier Pérez-Calvo, Pilar Martínez-Sánchez, Blanca Sánchez-González, Miguel-Angel Canales, Eulogio Conde, Alejandro Martín, Eva Arranz, María-José Terol, Antonio Salar, Dolores Caballero
• Journal: Haematologica (Haematologica) Vol. 98 Issue 10 Pg. 1563-70 (Oct 2013) ISSN: 1592-8721 [Electronic] Italy
• PMID: 23753021 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

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

Topics

• 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, drug therapy, epidemiology)
• Male
• Methotrexate (administration & dosage)
• Middle Aged
• Pilot Projects
• Prospective Studies
• Rituximab
• Treatment Outcome