A Phase 2 Multicenter Study of Siltuximab, An Anti-IL-6 Monoclonal Antibody, in Patients with Relapsed or Refractory Multiple Myeloma

• Published in: Blood 2011-11, Vol.118 (21), p.3971-3971
• Main Authors: Voorhees, Peter M., Manges, Robert F, Sonneveld, Pieter, Jagannath, Sundar, Somlo, George, Krishnan, Amrita, Lentzsch, Suzanne, Frank, Richard C, Zweegman, Sonja, Wijermans, P.W., Rijnbeek, Britte, Qin, Xiang, Cornfeld, Mark J., Xie, Hong, Thomas, Sheeba K.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V118.21.3971.3971

Abstract 3971 Although outcomes have improved for patients (pts) with multiple myeloma (MM), relapsed/refractory MM remains associated with short survival and constitutes an unmet medical need. Glucocorticoids (GCs) are an important component of MM therapy; however, resistance is common. In preclinical models, interleukin-6 (IL-6) promotes the proliferation and survival of MM cells in the context of the bone marrow microenvironment and protects these cells from GC-induced apoptosis. Therefore, blocking IL-6 may disrupt resistance and restore sensitivity to GCs. Here, we report the final results from a Phase 2 open-label, non-randomized study that evaluated the safety and efficacy of siltuximab (S), a monoclonal antibody targeting soluble human IL-6, in combination with high-dose dexamethasone (D) in pts with relapsed and relapsed/refractory MM. Pts with measurable, secretory disease who had received at least 2 prior lines of therapy, one of which contained bortezomib, and progressed during or after their last line of treatment were eligible. Other key eligibility criteria included a creatinine clearance ≥20 mL/min, platelets ≥50,000/mm3, and neutrophils ≥1,000/mm3. S was administered 6 mg/kg IV on days 1 and 15 of a 28-day cycle and oral D 40mg once daily, on days 1–4, 9–12, and 17–20 for a max of 4 cycles; days 1–4 for subsequent cycles. The first 14 pts received S alone for the initial 1 to 2 cycles; 10 pts had D added for progressive disease post-Cycle 1 or suboptimal response post-Cycle 2. 39 subsequent pts received S+D concurrently as none of the first 14 pts achieved ≥PR while on S monotherapy. The primary endpoint was overall response rate (ORR, CR+PR) using EBMT criteria. Secondary endpoints were time to progression (TTP), progression-free survival (PFS), overall survival (OS), and incidence of AEs and SAEs. Forty-nine pts received S+D. The median age was 65 yrs (range 43–89) and 43% of pts were female. The median disease duration was 4 yrs (range 0.7–13.2). Pts were heavily pretreated, having received prior bortezomib (100%), steroids (100%), IMIDs (90%), alkylating agents (91%) and ASCT (65%). The median number of prior lines of therapy was 4 (range 2–9); 86% had disease that was refractory to the last prior line. Of the 44 pts with prior D exposure, 32 (73%) were refractory to the last D-containing regimen. The median duration of therapy was 4 cycles (99 days). Of the 47 pts evaluable for response, the ORR by EBMT criteria was 17% (0 CRs, 8 PRs)