Nephrotic syndrome is considered a disease caused by an interplay of immunological stimuli with adaptive immunity(CD80/CD40) as trigger and Treg in the mid between co-stimulatory molecules and effectors. The positive effect of drugs blocking CD20 maturation in SDNS suggests a main role of these cells in regulating the system. One possible explanation of proteinuria resolution by anti-CD 20 in most but not all patients with SDNS/MDNS is that some CD20 cells may escape the inhibition and mature in some cases to plasmacells. On this basis, it seems reasonable to consider the association of two drugs, one targeting CD20 and one targeting plasmacells in order to block the stimulatory cascade at more sites. There are recent positive evidences from the association of 2 monoclonal antibodies that block maturation of CD20 at different steps. One study utilized the humanized anti-CD20 antibody obinutuzumab(single dose 1,000 mg 1.73m2) in combination with the anti-CD38 (plasmacells) monoclonal antibody daratumumab (1,000 mg 1.73m2)18 in patients who relapsed after conventional treatments with Prednisone, rituximab and CNI and developed dependence to the combination of more than 2 drugs (MDNS). A cohort of 14 patients treated with the above association were included in a retrospective analysis: all of them suspended oral drugs, 5 out of 14 presented recurrence of proteinuria after about 10 months, 9 out of 14 were in stable remission after 20 months. Therefore, the use of 2 monoclonal antibodies in low doses is potentially valuable considering the positive results and also taking in account the safety of the treatment. While it is not possible to discern the separate effects of obinutuzumab and daratumumab when given together, the preliminary positive results of their combination may open new ways in the treatment of nephrotic syndrome and supports the necessity of new studies in those patients who require more than one drug to maintain remission. The investigators hypothesize that rituximab in place of obinutuzumab (not available in Italy for the use in nephrotic syndrome) with daratumumab could produce the same positive effects in MDNS and MRNS.~The Dual 1 is a before-after clinical trial testing the superiority of rituximab plus daratumumab in maintaining drug free disease remission in patients with multi-drug dependent nephrotic syndrome.
Nephrotic syndrome is considered a disease caused by an interplay of immunological stimuli with adaptive immunity(CD80/CD40) as trigger and Treg in the mid between co-stimulatory molecules and effectors. The positive effect of drugs blocking CD20 maturation in SDNS suggests a main role of these cells in regulating the system. Multidrug dependent, multidrug resistant nephrotic syndrome as well as post transplant FSGS recurrence patients can be considered difficult to treat patients and the association of two drugs, one targeting CD20 and a targeting plasmacells can be use in order to block the stimulatory cascade at more sites.