We have previously reported that normal B lymphocytes in lymph nodes and peripheral blood of patients with Hodgkin’s disease (HD) express CD40 ligand (CD40L) and CD30 ligand (CD30L). Both ligands can activate NF-kb and promote
We have previously reported that normal Blymphocytes in lymph nodes and peripheral blood of patients with Hodgkin’sdisease (HD) express CD40 ligand (CD40L) and CD30 ligand (CD30L). Both ligandscan activate NF-kb and promote Reed-Sternberg (RS) cell survival. Therefore, wehypothesized that elimination of B lymphocytes from HD lesions may deprive theRS cells of important growth signals and may result in tumor regression.
To examine this hypothesis, we treated patients with relapsedclassic HD with 375 mg/m2 of rituximab (Rituxan) IV every week for 6 consecutiveweeks. Patients were eligible if they had relapsed classic HD, regardless ofCD20-antigen expression on RS cells, and had had at least two prior treatmentregimens. Patients were excluded if they were pregnant women, had lymphocytedepletion or lymphocyte-predominant histology, were infected with HIV, or hadcentral nervous system involvement by lymphoma.
Objective tumor response was assessed after completion of sixdoses. Eighteen patients with nodular sclerosis histology are enrolled, 15 ofwhom have completed the planned therapy and are evaluable for response. CD20antigen was expressed by the RS cells in 5 patients. Patient age ranged between17 and 66 years and the number of prior treatment regimens ranged between 2 and7 (median: 5 regimens). Thirteen patients had prior bone marrow transplantation.Seven patients had disease limited to lymph nodes and 8 had disease involvinglymph nodes plus lungs and/or liver.
Three patients (20%) had major responses (2 partial and 1complete [unconfirmed]). All responding patients had disease limited to lymphnodes and the RS cells did not express CD20. Six additional patients had stabledisease, 2 of whom experienced resolution of B symptoms.
CONCLUSION: Rituximab therapy, possibly by eliminating normal Blymphocytes from HD patients, can result in major clinical responses and symptomimprovement.