Final Analysis of Phase II Study of CHOP/CHOEP-14 Followed by Consolidation with Alemtuzumab in Untreated Aggressive T-Cell Lymphomas (DSHNHL 2003–1).

The clinical course of systemic T-cell Non Hodgkin lymphomas (T-NHL) is unfavourable in comparison to aggressive B-NHL. Treatment with standard CHOP-like protocols results in long-term remissions of approx. 30%. The moAb Alemtuzumab (CAM) against CD 52 shows promising activity in T-NHL, although its use especially in heavily pretreated patients (pts) is complicated by infections. To answer the question, whether addition of CAM to standard chemotherapy is feasible in previously untreated aggressive T-NHL pts, the German High Grade Non-Hodgkin’s Lymphoma Study Group (DSHNHL) initiated a prospective multicenter phase II trial. Six cycles of either CHOEP-14 (< 60 y) or CHOP-14 (> 60 y) with G-CSF support were followed by a short consolidation course with CAM, provided either a CR or good PR had been achieved by chemotherapy. Inclusion criteria were: histology of PTCL-NOS, AILD, intestinal T-NHL, anaplastic large cell T-NHL (ALK-); age 18 – 70 y; all IPIs; ECOG performance status 0 – 3. Primary endpoint was feasibility of the therapy, secondary endpoints were remission rate, treatment-related mortality, event-free (EFS) and overall survival (OS). CAM was given at a total dose of 133 mg over 4 weeks. Prophylaxis against pneumocystis carinii and herpes infections was mandatory during CAM therapy and continued until CD 4-cells were > 200/μl. CMV-positive pts were monitored weekly (pp65, CMV-PCR). Between 07/2003 and 07/2006 41 pts were enrolled, most of them with PTCL-NOS (51.2%) and AILD (26.8%). According to the reference histology, 4 pts did not fulfill the inclusion criteria (3 ALK+, 1 nasal type), but were included in the intent-to-treat (ITT) analysis. Median age was 55 y. Although there was a well-balanced distribution between IPI scores 0–1 (39%), 2 (24.4%) and 3 (34.1%), a considerable number of pts presented with unfavourable prognostic features: elevated LDH (48.8%), stage III/IV (63.4%), extranodal involvement (46.3%), B-symptoms (40%), bone marrow involvement (14.6%) and bulky disease (12.2%). Eight pts did not respond to chemotherapy and were treated off study with various salvage protocols. Twenty nine pts (70.7%) received CAM. The main grade 3–4 toxicities during CAM therapy were: infection (13.7%), leukocytopenia (11.5%), allergy (3.7%). There was no treatment-related death. The response to therapy (ITT) was: 58.5% CR/CRu, 2.4% PR, 9.8% no change, 29.3% progressive disease. After a median follow-up of 25 months, 15 pts have died, 13 of them due to lymphoma and/or salvage therapy complications. The estimated EFS at 24 months is 32% in the whole ITT population and 43.9% in the pts, who received CAM (OS: 61% and 73.6%, respectively). Taken together, combination of CHOP/CHOEP-14 with a short course of CAM consolidation is a feasible therapeutic option. Adverse effects are partially severe, but manageable. The high rate of non-responders to chemotherapy suggests inclusion of CAM as part of the initial cytostatic protocol, which is currently evaluated by the intergroup phase III trial ACT-2.