A Phase II Immunochemotherapy Study with Alemtuzumab, Fludarabine, Cyclophosphamide, and Doxorubicin (Campath-FCD) in Peripheral T-Cell Lymphomas.

The majority of entities of peripheral (mature) T-cell lymphomas (PTCL) have an unfavourable prognosis as compared to aggressive B-cell lymphomas. This difference has become even more pronounced since the introduction of CD20 antibodies in B-cell lymphoma therapy. The purpose of the present study was to investigate the feasibility and efficacy of the combination of the monoclonal antibody alemtuzumab with chemotherapy consisting of fludarabine, cyclophosphamide and doxorubicin in PTCL. Patients were treated with alemtuzumab 3, 10, 30, 30 mg, days 1–4, fludarabine 25 mg/m² days 2–4, cyclophosphamide 600 mg/m² day 3, and doxorubicin 50 mg/m² day 4. Initially, patients with primary diagnosis, with first relapse, or with primary refractory disease were included. Excluded were patients with primary cutaneous T-cell lymphomas and ALK-positive large cell anaplastic T-cell lymphomas. So far, 37 patients have been included and 30 are evaluable for response and toxicity: 13 patients with PTCL-unspecified, 9 with angioimmunoblastic lymphoma, two with ALK negative anaplastic large cell lymphoma, two with enteropathy-associated T-cell lymphoma, two with nasal-type NK-/T-cell lymphoma, one with an NK-cell lymphoma, and one with a T-PLL. 19/30 patients were enrolled with primary diagnosis of PTCL and 11/30 patients with relapse or refractory disease. The median age was 56 years (range 21–77); 69% of the patients had an intermediate high or high prognostic score according to the international prognostic index. In patients with primary diagnosis the remission rate was 63% (12/19; CR 58%, PR 5%), four patients were primary progressive, and three patients dropped out because of treatment associated complications. Of the 12 responding patients 10 are in ongoing remission at 2+, 2+, 3+, 6+, 12+, 14+, 26+, 27+, 38+, and 39+ months, respectively. Two patients relapsed after being in CR for 23 and 34 months, respectively. In the group of relapsed or refractory patients three CR and two PR (45% overall response) were observed. The main toxicity was leukocytopenia (65% grade III and IV of all evaluable treatment cycles), other grade III and IV toxicities included anemia (17%), thrombocytopenia (35%), infections (16%), pruritus/skin reactions (11%), nausea/emesis (6%), mucositis (4%), and cardiac toxicity (4%, two patients with relapsed disease after pre-treatment with CHOP-like regimens developed severe heart failure and died). 12 (40%) patients reactivated CMV, however, 10 without developing CMV-related disease. In conclusion, the combination is an effective first-line regimen for peripheral T-cell lymphoma, however, regarding the general outcome a longer follow-up period of a larger patient population is required. Because the results were not convincing in relapsed and refractory disease and because of two heart failures in this group, the study was closed for relapsed and refractory patients, but is ongoing for first-line treatment of peripheral T-cell lymphomas.