Anti-epidermal growth factor receptor antibody cetuximab in refractory or relapsed multiple myeloma: a phase II prospective clinical trial

Abstract

Cetuximab is an anti-epidermal growth factor receptor (EGFR) antibody approved for the treatment of colorectal and head and neck cancer [1]. EGFR is also expressed on multiple myeloma (MM) plasma cells and bone marrow stromal cells (BMSCs) [2,3]. Th e inhibition of EGFR has been shown to induce apoptosis in myeloma cells revealing a synergistic eff ect with dexamethasone [2]. Th us, the anti-EGFR antibody cetuximab might be of clinical benefi t in the treatment of MM, especially in combination with dexamethasone. Here, we report the fi nal results of the fi rst clinical trial with an anti-EGFR antibody in MM, the EMMA1 trial. Eligible patients were adults with recurrent or refractory Durie – Salmon stage II or III MM who were not candidates for or had already undergone high-dose chemotherapy and autologous stem cell transplant (ASCT). Review boards at participating institutions approved the study, which was conducted according to the International Conference on Harmonization and the Guidelines for Good Clinical Practice. Written informed consent was obtained from all patients in accordance with the Declaration of Helsinki 1995. EMMA1 was an open-label, non-randomized phase II study (ClinicalTrials.gov Identifi er: NCT00368121). Th e primary endpoint was overall response rate (ORR) after 16 weeks of treatment. Secondary endpoints included adverse events during treatment, freedom from treatment failure (FFTF), progression-free survival (PFS) and overall survival (OS). Clinical benefi t rate (CB, defi nition: at least stable disease [SD]) was calculated in post hoc analyses. Patients received a cetuximab loading dose of 400 mg/m 2 intravenously on day 1 followed by weekly administrations of 250 mg/m 2 intravenously. Patients achieving at least SD after 4 weeks or responding to treatment within 8 weeks received cetuximab for a total of 16 weeks. Patients not achieving stable disease after 4 weeks or a response after 8 weeks of cetuximab treatment additionally received 20 mg oral dexamethasone on days 1 – 3 of each 7-day cycle. Patients achieving a response or stable disease after 16 weeks of treatment could continue study medication for an additional 6 months (patients receiving cetuximab alone) or for an additional 3 months (patients receiving cetuximab plus dexamethasone; dexamethasone was tapered down according to local guidelines). Responding patients who relapsed during the follow-up period of 2 years were off ered a second treatment with cetuximab following initial study guidelines. Tumor response was monitored by quantitative serum