A phase II study of bortezomib in combination with intensified CHOP-like regimen (ACVBP) in patients with previously untreated T-cell lymphoma: Results of the GELA LNH05–1T trial

Abstract

8554 Background: Patients with peripheral T/NK cell lymphomas (PTCL) still have a dismal prognosis with 5-yr survival less than 30% in most cases. No alternative regimen has been proven superior to CHOP so far. This multicenter phase II study was carried out to assess efficacy and safety of bortezomib in combination with an intensified CHOP-like regimen. Methods: Pts aged 18 to 65 yrs with previously untreated PTCL were planned to receive 4 bi-monthly cycles of ACVBP (doxorubicine 75 mg/m2 D1, cyclophosphamide 1200 mg/m2 D1, vindesine 2 mg/m2 D1 and D5, bleomycine 10 mg D1 and D5 and prednisone D1 to D5) followed by a sequential consolidation consisting of HD methotrexate (2 courses), etoposide + ifosfamide (4 courses) and cytarabine (2 courses) at 2 weeks intervals. Bortezomib 1.5 mg/m2 was administered at D1 and D5 of each ACVBP cycle, and then at D1, D8 and D15 every 4 weeks during consolidation phase for a total of 20 injections during the whole treatment. Results: 57 eligible pts (M 38, F 19, median age 52.5 yrs) with mostly AITL and PTCL NOS subtypes were enrolled between January 2006 and November 2007; 78% had stage III-IV disease and 53% had aaIPI ≥ 2. Forty six pts (81%) have completed induction treatment with ACVBP and only 28 (49%) the consolidation phase, mainly for disease progression. The CR + CRu rate was 45% after induction and 46% after consolidation. As of November 14th, 2008, 22 pts (39%) have died, mostly from lymphoma. The median percentage of planned dose of bortezomib received was 98% during ACVBP induction where the vinca alkaloid used was vindesine, and ranged from 90 to 95% during the consolidation courses. The dose intensity of bortezomib was 84.3% during induction, similar to that of doxorubicine and cyclophosphamide. Thrombocytopenia was more pronounced than previously observed with ACVBP alone but no life-threatening hemorrhagic event occurred. Conclusions: The combination of bortezomib with ACVBP is feasible without neurological or platelet unexpected toxicities. The response rate of such a regimen in PTCL does not appear higher than previously observed with ACVBP alone in our historical cohort. No significant financial relationships to disclose.