Background: Relapsed/refractory MM constitutes a specific and unmet medical need with poor overall response and survival. Interleukin-6 (IL-6) plays an important role in MM cell proliferation, survival, and corticosteroid resistance and previous studies have shown clinical benefit from anti-IL-6 therapy. We therefore evaluated the combination of CNTO328, a chimeric monoclonal antibody with high affinity for human IL-6, and dexamethasone (dex) in pts with relapsed/refractory MM. Methods: Pts were treated with 6 mg/kg CNTO328 IV Q2 weeks. Oral dex (40mg) was given once daily, days 1-4, 9-12, and 17-20 for a max of 4 cycles; and on days 1-4 for subsequent cycles. Inclusion criteria were > 2 prior lines of systemic therapy, creatinine clearance >20 ml/min, platelets >50,000/mm3, and neutrophils >1000/mm3. Primary endpoint was overall response with secondary endpoints of time to progression, incidence of AEs and SAEs. Results: Thirty-nine pts received at least 1 infusion of CNTO328 in combination with dex - median age 66 yrs (range 43-89), median disease duration 4.2 yrs (1-13), median lines of prior therapy 5 (2-9) including bortezomib (100%), IMIDs (87%), and ASCT (59%). The median duration of therapy was 3.3 months (0.5-21+). Of the 36 pts who were evaluable, the overall response rate (CR+PR+MR) using EBMT criteria was 31% (7PR, 4MR). An additional 4 uMR and 4 SD lasting > 3 months have been reported. PRs were durable; 6 out of 7 pts had responses ranging from 3 months to up to more than 1 year (with 1 still ongoing for more than 1 year). Duration of MRs ranged from 2-5 months. Responses were seen in pts relapsing after and refractory to at least one other prior treatment including bortezomib, IMIDs, or steroids. Median time to disease progression (PD) was 3.7 months (0.3-18+). Main reasons for treatment discontinuation were PD (24) and AEs (6). Hematologic toxicities Grade > 3 were common though not dose-limiting. Three pts had Grade > 3 infections considered reasonably related to CNTO328. Conclusions: CNTO 328 in combination with dex shows promising preliminary activity in this heavily pretreated patient population with an acceptable safety profile. Further investigation is ongoing.
|Number of pages||1|
|Journal||Journal of Clinical Oncology|
|Publication status||Published - 2009|
Voorhees, P. M., Manges, R. F., Somlo, G., Lentzsch, S., Jagannath, S., Sonneveld, P., ... Thomas, S. (2009). A phase II multicenter study of CNTO 328, an anti-IL-6 monoclonal antibody, in patients (pts) with relapsed or refractory multiple myeloma (MM). Journal of Clinical Oncology, 1), 8527.