Rituximab in CD20 Positive Multiple Myeloma: A Prospective Study from the IFM Group.

Abstract Multiple myeloma (MM) is a heterogenous disease. A strong association between small mature plasma cell morphology, t(11;14) and CD20 expression has been described in approximately 10% of the patients with MM (Robillard et al, Blood 2003). In this subgroup of patients with MM expressing CD20, rituximab (anti-CD20 chimeric monoclonal antibody) could target the antigen and could have a clinical impact. Thus we conducted a prospective phase II trial of 4 weekly IV infusions of 375 mg/m2 rituximab in patients with MM expressing CD20 on at least 33% of tumor cells. From 07/2004 to 02/2006, 14 consecutive patients, median age 65 years, with either stage I MM never pretreated (n = 7) or stage III MM in relapse or refractory after a median of 2 lines of therapy (n= 7) were treated. Immunophenotype using flow cytometry revealed that a median of 75% of tumor cells were expressing CD20 (range, 33–100%) at the onset of therapy. Responses were evaluated 3 months after therapy according to EBMT criteria. At the reference date of June 1st, 2006, a single patient, who had relapsed 8 months after a double autologous SCT, experienced a minor response, ongoing 18 months after rituximab therapy. At the time of rituximab therapy, 100% of its plasma cells were expressing CD20, and 3 months after treatment, bone marrow examination showed 0.6% of plasma cells, none of them expressing CD20. Five patients (1 with relapsed MM and 4 with stage I MM) experienced stable disease, ongoing for 3, 4, 4, 11 and 12 months, respectively. Three patients with stage I MM had stable disease but subsequently progressed 10, 11, and 15 months after therapy, respectively. The last 5 patients with relapsed MM did not respond to anti-CD20 therapy, despite partial clearance of CD20+ plasma cells in the bone marrow in 2 cases. Conversely in the 3 latter cases, the percentage of CD20+ plasma cells did not decrease despite rituximab therapy. Several factors have been described to explain resistance against rituximab in a variety of B-cell malignancies such as the level of CD20 expression, dissociated action of complement-dependent cytotoxicity and antibody-dependant cellular cytotoxicity, polymorphism in FcgammaRIIIA receptor, and may be inadequate dose schedule. These mechanisms could explain the marginal activity of rituximab as single-agent in CD20+ MM.