In diffuse large B-cell lymphoma (DLBCL), stromal signatures are predictive of outcome in newly diagnosed patients treated with R-CHOP. These signatures, termed 'stromal 1' and 'stromal 2' are associated with genes expressed by infiltrating mononuclear cells. The stromal 2 signature includes genes associated with angiogenesis and is associated with a poor outcome. Hence, targeting reactive cells in the microenvironment is a rational therapeutic strategy in DLBCL. In Hodgkin lymphoma (HL), the reactive macrophages surrounding Hodgkin Reed Sternberg (HRS) cells are associated with an adverse outcome and may provide survival signals. CD52 is highly expressed in many of these cells in the microenvironment and in most cases of DLBCL.
We combined alemtuzumab (a monoclonal antibody against CD52) with DA-EPOCH-R to target reactive cells in the microenvironment and positive tumor cells. Alemtuzumab (30 mgs on day 1) was administered intravenously before DA-EPOCH-R (as previously described) and responding patients received up to 6 cycles of therapy.
Characteristics of 28 patients accrued: median age (range) 44 (22–72); male sex 15 (54%); stage III or IV disease 20 (71%); median prior regimens (range) 2 (1–6); and prior autologous transplant 7 (25%). Enrolled histologies were HL 12 (43%); DLBCL 10 (36%); and primary mediastinal B-cell lymphoma 6 (21%). Responses by histological subtype are shown in the attached table. The regimen was particularly effective in patients with HL with a CR rate of 73%. At 12 months (with 21 months median potential follow-up), the OS and PFS probabilities for all patients were 68% and 18% respectively. Toxicities included: treatment related mortality (sepsis) in 1 patient; febrile neutropenia in 16%; and grade 4 thrombocytopenia 15% of cycles. CMV reactivation was observed in 52% of patients in the setting of anti-viral prophylaxis.
Combining alemtuzumab with DA-EPOCH-R is feasible. Patients with a diagnosis of HL had a very high complete response rate. Accrual continues.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.