Multicenter Phase II Study of the CyclOBEAP Regimen for Patients with Peripheral T-Cell Lymphoma with Analysis of Biomakers.

Abstract 2795

Peripheral T-cell lymphoma (PTCL) is more aggressive and has a poorer prognosis than diffuse large B-cell lymphoma (DLBCL). In particular, PTCL, not otherwise specified (PTCL, NOS) is not responsive to conventional chemotherapies. The usefulness of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation has been reported, although a recent study did not confirm this result. More recent study, however, suggested that intensified regimens may indeed yield superior results to CHOP. We previously administered the CyclOBEAP (cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, prednisolone) regimen to patients with DLBCL, and reported its safety and efficacy.

nm23-H1 was originally identified as a protein that was expressed at a lower level in metastatic cancer cells. The nm23 genes play critical roles in cellular proliferation, differentiation, oncogenesis, and tumor metastasis. We previously reported that the serum nm23-H1 level was significantly higher in patients with aggressive lymphoma than in healthy controls, and that a high nm23-H1 level was associated with poor prognosis in patients with aggressive lymphoma. We previously examined cytoplasmic nm23-H1 expression in DLBCLs and found that the serum and cytoplasmic nm23-H1 levels were significant prognostic factors in DLBCLs.

Here, we report the results of a multicenter phase II study of the CyclOBEAP regimen for patients with PTCLs [anaplastic large-cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AILT), and PTCL, NOS]. This was a prospective, single-arm phase II trial in the Adult Lymphoma Treatment Study Group (ALTSG) in Japan. Patients were enrolled in the study between April 1998 and March 2006. Patients aged between 18 and 60 years who were in the low-intermediate (L-I), high-intermediate (H-I), or high (H) risk groups, were eligible for this study. The CyclOBEAP regimen was administered over a total period of 12 weeks. In the CyclOBEAP regimen, the dose intensities of cyclophosphamide, doxorubicin, and vincristine are equal to or higher than those in the CHOP regimen, and etoposide and bleomycin were added to the CHOP regimen. There were 84 eligible patients and the median age was 54 years. The median follow-up period was 82 months. A complete response was achieved in 77 patients (92%). The 5-year overall survival (OS) rate was 72% and progression-free survival (PFS) rate was 69%. The 5-year OS was 93% among the ALCL patients, 74% among the AILT patients, and 63% among the PTCL,NOS patients. Further evaluation of the 5-year PFS among the PTCL, NOS and AILT patients (n=70) according to the international prognostic index showed that the 5-year PFS in patients with L-I, H-I or H risk was 77.4%, 48.6% and 25%, respectively (P=0.011). When the patients were divided according to the prognostic index for PTCL (PIT), the 5-year OS and PFS rates did not significantly differ among the risk groups. We next examined the survival curve of patients with PTCL in whom soluble interleukin-2 receptor data were available. The 5-year survival rates of the high (≧2000 IU/ml) and low soluble interleukin-2 receptor groups (<2000 IU/ml) were 60.2 and 69.5%, respectively (p=0.75), with PFS rates of 51.1 and 70.5% (p=0.25). As for nm23-H1 expression in the PTCL, NOS and AILT patients in the present study, the 5-year OS of the nm23-H1-positive group was 46.7% and that of the nm23-H1-negative group was 83.3%, indicating that the nm23-H1-positive group showed significantly poorer prognosis (p = 0.0007). Univariate analysis showed that bone marrow involvement, bulky lesion, serum LDH level, serum albumin level and nm23-H1expression were significant prognostic factors, and in multivariate analysis, nm23-H1 expression was a significant independent prognostic factor. Grade 4 neutropenia was observed in 80 patients and thrombocytopenia in 9 patients.

Our results suggest that the CyclOBEAP therapy is safe and effective for the treatment of PTCLs. Furthermore, nm23-H1 protein expression may be an important prognostic factor in PTCLs.