Efficacy of alemtuzumab (ALZ) in combination with dose-adjusted EPOCH (DA-EPOCH) in untreated nodal peripheral T-cell lymphoma (PTCL).

Abstract

8051 Background: The survival of patients (pts) with PTCL (excluding ALCL) is disappointing following anthracycline-based therapy and novel approaches are needed. In diffuse large B-cell lymphoma, the addition of anti-CD20 therapy to CHOP has significantly improved outcome and we investigated if in PTCL, adding ALZ – which targets CD52, expressed on most PTCLs – was feasible and improved outcome. Methods: This was a single-center phase I/II trial of ALZ, in combination with DA-EPOCH in patients with treatment-naïve CD52+ PTCL. The MTD of 30 mg ALZ was combined with DA-EPOCH for phase II evaluation resulting in an intention-to-treat population (ITTP) of 30 pts. Results: Patient (n=30) characteristics: median (range) age 50 (17-77); M:F 1:1; Stage III/IV 27 (90%); IPI ≥2 22 (73%). Histologies: ATLL 11 (37%), PTCL NOS 6 (20%), AITL 5 (16%), Hepatosplenic 3 (10%), Peripheral T NK cell 2 (7%), Other 3 (10%). At 67 months median follow-up, 11 patients were alive, 10 disease-free. Median overall (OS) and event-free survivals (EFS) were 15.4 and 6.7 months respectively. Outcome was substantially better for pts with ‘nodal’ (AITL, PTCL-NOS, Other) compared to ‘non-nodal’ (ATLL and ‘extranodal’ histologies) PTCL subtypes. 3-year OS for the two groups was 58.3% and 27.8% respectively (p=0.082); 3-yrs EFS was 50% (median 27.0 months) and 22.2% (median: 5 months) respectively (p=0.041). Half of the ‘nodal’ PTCL pts had sustained long-term complete remissions demonstrated by a plateau in the EFS curve at 27 months. There were 3 treatment related deaths: 2 from neutropenic sepsis; 1 from toxoplasma. Other toxicities included CMV and BK virus reactivation in 53% and 30% respectively. Febrile neutropenia was seen in 20% and grade 4 thrombocytopenia in 12 % of cycles. Conclusions: Although it has significant infectious toxicity, ALZ 30mg and DA-EPOCHin untreated PTCL is feasible and associated with a long-term favorable outcome in nodal but not extranodal or leukemic PTCL. A phase III study of ALZ 30mg with anthracycline-based therapy is ongoing and we await the results with interest.