Combination Chemoimmunotherapy Using Alemtuzumab, Fludarabine, Cyclophosphamide, and Doxorubicin (Campath-FCD) Is an Effective First-Line Regimen in Peripheral T-Cell Lymphomas.

Peripheral (mature) T-cell lymphomas (PTCL) are represented by distinct lymphoma entities, many of which with a rather unfavourable clinical outcome as compared to B-cell lymphomas. Standard treatment regimens have not been established, except in primary cutaneous T-cell lymphomas (PCTCL). With regard to the unfavourable prognosis we designed a treatment protocol using chemoimmunotherapy in peripheral T-cell lymphomas except PCTCL and ALK-positive large cell anaplastic T-cell lymphomas, consisting of alemtuzumab 3, 10, 30, 30 mg, days 1–4, fludarabine (Flu) 25 mg/m² days 2–4, cyclophosphamide (CP) 600 mg/m² day 3, and doxorubicin (Dox) 50 mg/m² day 4. Included were patients with primary diagnosis or with first or second relapse. Rationales for this regimen were proven efficacy of CP and Dox in T-cell lymphomas, high efficacy of Flu and CP (FC) in other lymphomas and the possible synergism of antibodies with cytotoxic drugs. So far, 23 patients have been included, 18 are evaluable for response and toxicity. Of the latter, 10 patients were diagnosed with PTCL-NOS, 5 with AILD, one with enteropathy-associated T-cell lymphoma, one with NK-cell lymphoma, and one with T-PLL. 9 patients were enrolled with primary diagnosis and 9 patients in relapse. The median age was 60 years (range 21–77); the median non-age adjusted IPI 2.5 (0–4), 2 in patients with primary diagnosis and 3 in patients with relapse. The overall response rate was 61% (11/18). In patients with primary diagnosis the CR rate was 78% (7/9), one patient achieved no change, and one patient died from treatment associated complications before response could be evaluated. All responding patients are in ongoing CR at 2+, 2+, 6+, 11+, 15+,16+, and 17+ months. In the group of relapsed patients one CR and 3 PR (44%) were observed. The main toxicity was leukocytopenia (81% grade III and IV of all evaluable treatment cycles), other grade III and IV toxicities included anemia (18%), thrombocytopenia (39%), infections (18%) nausea/emesis (9%), and allergic reactions (4%). Ten (56%) patients reactivated CMV without CMV-related disease and one patient with suspected CMV-peumonia. In conclusion, this is the first study demonstrating that alemtuzumab can be integrated into a triple-agent chemotherapy regimen. The combination is effective in the first-line treatment of peripheral T-cell lymphomas, however, regarding the general outcome a longer follow-up period of a larger patient population is required.