Siltuximab monotherapy improves progression free survival compared to rituximab-based therapies in patients with idiopathic multicentric Castleman disease; indirect comparison of studies using single-arm metanalysis method and the generalized linear mixed model.

Siltuximab is the only approved treatment for idiopathic multicentric Castleman Disease but in many countries the only available treatment is rituximab based. We are performing an indirect comparison of rituximab-based regimens (RBR) and siltuximab by using single arm meta-analysis and the generalized linear mixed model methods comparing outcome in five significant clinical end-points (CR, PR, ORR, 2ysPFS and 2ysOS). Patient's data were extracted from 14 cohort or phase I and II trials conducted with siltuximab (n = 387 pts) and six cohort studies treating iMCD patients with rituximab (n = 138 pts). Response rates and depth of response is similar between the two arms of the study but 2ys PFS is significantly better with siltuximab monotherapy. Using the generalized linear mixed model in order to provide an indirect comparison of odds to achieve the 2yPFS end-point, the reported OR is 0,358, 95% CI (0,147-0,873) and p = 0,027 favoring siltuximab over rituximab-based regimens (RBR). This is the major finding of our study and to our knowledge is the first time that in a big cohort of patients siltuximab is proved more effective compared to RBR.