SP164RITUXIMAB THERAPY IN PATIENTS WITH PRIMARY AND SECONDARY GLOMERULONEPHRITIS: RELATIONSHIP BETWEEN CLINICAL RESPONSE AND CD19+ TREND

Abstract

Introduction and Aims: Rituximab has been shown to be an effective therapy in a number of primary glomerulonephritis and in immune-mediated systemic disease with renal involvement. Once administered with the schedule used in lymphoma (i.e. 4 administrations, 375 mg/m2), more recently it is administered as a single administration or using the rheumatologic dose regimen (2 administrations, 1 g). However, it is still unclear whether a single administration obtaining complete CD 19+ depletion may be enough to obtain a significant clinical response. Moreover, little is known for how long CD19+ persists following the single administration. Methods: Single centre, retrospective analysis of 18 patients (9 M/ 9 F; mean age 60.96 ± 14.21 years), treated with Rituximab in single or multiple dose for a variety of conditions (Membranous glomerulonephritis = 6; ANCA associated vasculitis = 3; Lupus nephritis = 3; HCV positive cryoglobulinemia = 5, focal segmental glomerular sclerosis = 1) between June 2009 and December 2013 (median follow up of 12.6 months, range 1.56 - 47.03 months). CD 19+ levels, serum creatinine, proteinuria and clinical manifestations of systemic disease were collected at baseline (first Rituximab administration) and during follow-up. Results: Rituximab therapy was decided because of refractory disease to more traditional therapies and absolute or relative contraindications. Patients received from one to four Rituximab infusions (mean 1.77) according to clinical needs and CD19+ trend over time. 4 patients received a rheumatologic dosing regimen. The mean dose for each Rituximab administration was 738.47 mg. with a mean cumulative dose of 991.45 mg (min 375 mg, max 3400 mg).Complete CD19+ depletion (CD19+ < 5 cell/ mm3) was obtained in all the patients; CD19+ returned to values ≥ 5 cell/mm3 in 13 patients after a mean of 7.87 months (min 3.6, max 19.9 months). In one patient with cryoglobulinemia, who was treated with 3 doses of Rituximab, complete CD19+ depletion was persistent during the whole follow-up.The trend of CD19+ was related to clinical manifestations in 9 out of 16 patients (two patients were excluded for inconclusive data).Treatment response (defined as significant improvement of clinical manifestations of the disease and/or proteinuria decrease and/or improvement in renal function) was obtained in 13 out of 16 patients.Drug administration was complicated by fever in one patient and atrial fibrillation in another one. 4 patients developed pneumonia following Rituximab administration and one patient had severe sepsis. One patient had a syncope two weeks after drug administration. Conclusions: Rituximab is an effective treatment option in adult patients suffering from primary and secondary glomerulonephritis. According to our limited experience, CD19+ depletion cannot always predict patient response to Rituximab and/or disease relapses, even if in some patients increased CD19+ levels may anticipate disease relapses.