Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial

Abstract

Janssen Research & Development.

Long-term CD38 saturation by daratumumab interferes with diagnostic myeloma cell detection

“…Since parallel receptor-saturation studies were not performed in the context of previous daratumumab trials, [3][4][5] only estimates from a kinetic model, but no in vivo target saturation data, were available. According to this model, daratumumab plasma concentrations of 236 µg/mL are necessary to achieve 99% CD38 saturation in vivo.…”

“…The 16 mg/kg dosing has shown superior outcomes and is certainly advisable due to relevant target-mediated clearance in patients with high tumor load at treatment initiation. Anna Oberle, 1 Anna Brandt, 1 Malik Alawi, 2 Claudia Langebrake, 3,4 Snjezana Janjetovic, 1 Christine Wolschke, 4 Kerstin Schütze, 5 Peter Bannas, 6 Nicolaus Kröger, 4 Friedrich Koch-Nolte, 5 Carsten Bokemeyer 1 and Mascha Binder…”

The next generation of novel therapies for the management of relapsed multiple myeloma

“…An open-label, international multicenter, Phase II trial enrolled patients with MM who were previously treated with at least three lines of therapy (including PI and IMiDs), or were refractory to both PI and IMiDs [39] www.futuremedicine.com median PFS was 3.7 months (95% CI: 2.8-4.6) and the median OS was 17.5 months (95% CI: 13.7-not estimable) [39]. Daratumumab was well tolerated; infusion reactions during the first cycle, fatigue and anemia of any grade were the most common AEs [39].…”

“…Daratumumab was well tolerated; infusion reactions during the first cycle, fatigue and anemia of any grade were the most common AEs [39].…”

Monoclonal antibodies for treating multiple myeloma - a new era, new safety considerations?

“…Most events occurred during the first infusion, and no patient discontinued treatment because of IREs [2]. Subsequently, a phase II study assessed daratumumab at 16 mg/kg in 106 relapsed/refractory MM (RRMM) patients: the ORR was 29%, the median PFS was 3.7 months, and only 5% of grade 3 IREs were observed [3]. Of note, these patients were heavily pretreated, almost all of them did not respond to therapy with IMiDs or PIs, they were refractory to alkylators or had relapsed after autologous stem transplantation.…”