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 Reed-Sternberg (RS) cell survival. Therefore, we hypothesized that elimination of B lymphocytes from HD lesions may deprive the RS cells of important growth signals and may result in tumor regression.
To examine this hypothesis, we treated patients with relapsed classic HD with 375 mg/m2 of rituximab(Drug information on rituximab) (Rituxan) IV every week for 6 consecutive weeks. Patients were eligible if they had relapsed classic HD, regardless of CD20-antigen expression on RS cells, and had had at least two prior treatment regimens. Patients were excluded if they were pregnant women, had lymphocyte depletion or lymphocyte-predominant histology, were infected with HIV, or had central nervous system involvement by lymphoma.
Objective tumor response was assessed after completion of six doses. Eighteen patients with nodular sclerosis histology are enrolled, 15 of whom have completed the planned therapy and are evaluable for response. CD20 antigen was expressed by the RS cells in 5 patients. Patient age ranged between 17 and 66 years and the number of prior treatment regimens ranged between 2 and 7 (median: 5 regimens). Thirteen patients had prior bone marrow transplantation. Seven patients had disease limited to lymph nodes and 8 had disease involving lymph nodes plus lungs and/or liver.
Three patients (20%) had major responses (2 partial and 1 complete [unconfirmed]). All responding patients had disease limited to lymph nodes and the RS cells did not express CD20. Six additional patients had stable disease, 2 of whom experienced resolution of B symptoms.
CONCLUSION: Rituximab therapy, possibly by eliminating normal B lymphocytes from HD patients, can result in major clinical responses and symptom improvement.