Table 5.
Summary of clinical trials and case series for siltuximab and tocilizumab in MCD
| Study | Design | Patient numbers and characteristics | Dose given (patients) | Median overall follow-up | ORR | OS | Median TTP |
|---|---|---|---|---|---|---|---|
| Siltuximab | |||||||
| Kurzrock et al89 | Phase I, open-label dose-finding study | 37 patients: • 35 MCD, 2 UCD • All HIV-negative • 1 HHV-8-positive |
• 3 mg/kg q2w (1) • 6 mg/kg q2w (2) • 12 mg/kg q3w (16) • 6 mg/kg qw (3) • 12 mg/kg q2w (3) • 9 mg/kg q3w (12) |
29.4 months | 86% | 92% for follow-up period | Not reached |
| van Rhee et al90 | Phase II, open-label randomized study | 79 patients: • All MCD • All HIV- and HHV-8-negative |
• 11 mg/kg q3w (53) • Placebo (26) |
14 months | 34% (vs 0% in placebo arm) | 100% at 1 year (though two patients in siltuximab arm and four patients in placebo arm subsequently died) | Not reached |
| van Rhee et al91 |
Extension of earlier Phase II study, in ongoing responders | 19 patients: • All MCD • All HIV- and HHV-8-negative |
• 11 mg/kg q3w (19) – 8 changed to extended dosing frequency (q6w) | 61 months | 100% sustained disease control | 100% for follow-up period | Not reached |
| Tocilizumab | |||||||
| Nishimoto et al92 | Multicenter, open-label study | 28 patients: • All MCD • All HIV-negative • 2 HHV-8-positive |
• 8 mg/kg q2w (28) | 15 months | 52% (nodal) 71% (biochemical) | 96% for follow-up period | Not reached |
| Matsuyama et al93 | Case series | Three patients: • All MCD • HIV and HHV-8 status not reported |
• 8 mg/kg q2w (3) | Not stated | 100% | Not stated | Not stated |
| Galeotti et al94 | Case series | Two patients: • All MCD • All HIV- and HHV-8-negative |
• 8 mg/kg q2w (2) | 3 years (Patient 1), 8 months (Patient 2) | 100% | 100% | Not reached |
| Nagao et al99 | Case series | Two patients: • All MCD • All HIV-and HHV-8-positive |
• 8 mg/kg q2w (2) | 4 years (Patient 1) and 1 year (Patient 2) | 100% | 100% for follow-up period – ongoing remission after rituximab | 15 weeks (Patient 1), 22 weeks (Patient 2) |
Abbreviations: MCD, multicentric Castleman disease; ORR, overall response rate; OS, overall survival; TTP, time to progression; HIV, human immunodeficiency virus; HHV-8, human herpesvirus-8; UCD, unicentric Castleman disease; qw, weekly; q2w, every 2 weeks; q3w, every 3 weeks; q6w, every 6 weeks.