Bortezomib in combination with CHOP as first-line treatment for patients with stage III/IV peripheral T-cell...

We performed a phase II study to evaluate the efficacy of bortezomib in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) as first-line treatment for patients with stage III/IV peripheral T-cell lymphomas (PTCLs) based on our phase I study results.

Patients received bortezomib on days 1 and 8 at a dose of 1.6 mg/m(2) in addition to CHOP every 3 weeks for a total of six cycles.

Forty-six patients were enrolled: PTCL, not otherwise specified (PTCL-NOS, n=16), extranodal NK/T-cell lymphoma, nasal type (ENKTL, n=10), angioimmunoblastic T-cell lymphoma (AITL, n=8), ALK-negative anaplastic large-cell lymphoma (ALCL, n=6), cutaneous T-cell lymphoma (CTCL, n=5) and hepatosplenic T-cell lymphoma (n=1). Thirty patients achieved complete response (CR, 65%) and the overall response rate was 76% (35/46). Although the CR rate of ENKTL was only 30% (3/10), three subtypes of PTCLs (PTCL-NOS, AITL and ALCL) showed 87% of overall response rate (ORR) (26/30) and 73% of CR rate (22/30). However, the 3-year overall survival and progression-free survival were 47% and 35%, respectively due to frequent relapse after remission. Grade 3/4 leucopenia was the most frequent toxicity whereas neurotoxicity was tolerable: grade 1 or 2 of peripheral neuropathy.

The combined treatment of bortezomib and CHOP is an effective and feasible regimen for advanced-stage PTCLs other than ENKTL, with acceptable toxicity. However, future studies exploring new drug combinations are warranted to overcome relapse after remission.