Randomized, open label, phase 2 study of siltuximab (an anti IL 6 mAb) and bortezomib melphalan prednisone versus bortezomib-melphalan-prednisone in patients with newly diagnosed multiple myeloma
Mené sur 106 patients atteints d'un myélome multiple récemment diagnostiqué, cet essai de phase II évalue l'efficacité et la toxité de l'ajout de siltuximab, un anticorps monoclonal anti IL-6, à un traitement combinant bortezomib, melphalan et prednisone
Résumé en anglais
As interleukin (IL)-6 is considered important in the proliferation of early multiple myeloma (MM), we hypothesized that the addition of the anti-IL-6 monoclonal antibody siltuximab (S) to the VMP (bortezomib-melphalan-prednisone) regimen would improve outcomes in transplant-ineligible patients with newly diagnosed MM. One hundred and six patients were randomized to receive 9 cycles of VMP or VMP+siltuximab (11 mg/kg every 3 weeks) followed by siltuximab maintenance. Baseline characteristics were well balanced except for IgA subtype and 17p deletions. With a CR rate of 27% on S+VMP and 22% on VMP, the study did not confirm its hypothesis that the addition of siltuximab would increase CR rate by at least 10%. Overall response rate was 88% on S+VMP and 80% on VMP and at least VGPR rates were 71% and 51% (P=0.0382), respectively. Median progression-free survival (17 months) and 1-year overall survival (88%) were identical in the two arms. Grade ≥3 adverse event incidence was 92% on S+VMP and 81% on VMP (P=0.09) with trends towards more hematologic events and infections on S+VMP. Maintenance therapy with siltuximab was well tolerated. In conclusion, the addition of siltuximab to VMP did not improve CR rate nor long-term outcomes. This study was registered at http://clinicaltrials.gov as NCT00911859.
