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Phase 2 trial of rituximab and bortezomib in patients with relapsed or refractory mantle cell and follicular lymphoma.
- Source :
-
Cancer (0008543X) . 6/1/2011, Vol. 117 Issue 11, p2442-2451. 10p. 3 Charts, 4 Graphs. - Publication Year :
- 2011
-
Abstract
- BACKGROUND: In vitro studies in mantle cell lymphoma (MCL) cell lines and patient-derived cells have demonstrated synergistic apoptosis with combined rituximab and bortezomib (R-bortezomib) compared with single-agent bortezomib. Therefore, the authors of this report evaluated R-bortezomib in a preclinical model and in a phase 2 clinical trial. METHODS: A Hu-MCL-severe combined immunodeficiency (SCID) model engrafted with the Jeko cell line was treated with R-bortezomib, bortezomib, or rituximab. Twenty-five patients with relapsed follicular lymphoma (n = 11) and MCL (n = 14) received 375 mg/m² rituximab on Days 1 and 8 and 1.3 to 1.5 mg/m² bortezomib on Days 1, 4, 8, and 11 every 21 days for a median of 3 cycles (range, 1-5 cycles). RESULTS: R-bortezomib resulted in a statistically significant improvement in overall survival in Hu-MCL-SCID mice. In the clinical trial, the overall response rate was 40% in all 25 patients, 55% in patients with follicular lymphoma, and 29% in patients with MCL. The estimated 2-year progressionfree survival (PFS) rate was 24% (95% confidence interval [CI], 10%-53%) in all patients and 60% (95% CI, 20%-85%) in responding patients. Thirteen patients (52%) developed grade 3 neurotoxicity, which consisted of constipation/ ileus, sensory or motor neuropathy, or orthostatic hypotension. Patients who were heterozygous for the CD32a (Fcc receptor IIa) 131 histidine (H) to arginine (R) polymorphism had a significantly decreased PFS (P = .009) after R-bortezomib compared with HH and RR homozygotes. CONCLUSIONS: R-bortezomib had significant activity in patients with relapsed or refractory follicular lymphoma and MCL, although an unexpectedly high incidence of grade 3 neurologic toxicity was a potential limiting factor with this combination. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0008543X
- Volume :
- 117
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Cancer (0008543X)
- Publication Type :
- Academic Journal
- Accession number :
- 60694328
- Full Text :
- https://doi.org/10.1002/cncr.25792