A Phase II Clinical Trial of the Anti-EGFR Antibody Cetuximab in Patients with Refractory or Relapsed Multiple Myeloma: Final Results, (2011)

Abstract Abstract 3965 INTRODUCTION: So far, monoclonal antibodies have not yielded convincing therapeutic success in multiple myeloma (MM). Therefore, the discovery of an effective targeted antibody against MM would open new perspectives for patients with relapsed or refractory MM and for the combination with established therapies. Cetuximab is an anti-epidermal growth factor receptor (EGFR) antibody. EGFR is also expressed on multiple myeloma (MM) plasma cells and bone marrow stromal cells. Recently, the inhibition of EGFR by small molecule inhibitors has been shown to induce apoptosis in primary myeloma cells revealing a synergistic effect with dexamethasone. Therefore, the anti-EGFR antibody cetuximab might be of clinical benefit in the treatment of MM, especially in combination with dexamethasone. Here we show the final results of the first clinical trial with an anti-EGFR antibody in MM. METHODS: Cetuximab was administered once weekly in standard dose to patients with refractory or relapsed MM who had previously received at least one line of prior treatment including autologous stem cell transplant (ASCT). Patients who still were candidates for ASCT were not included. Dexamethasone 20 mg on day 1–3 of each cycle was added starting week 5 in case of tumor progression or week 9 if no partial response (PR) or complete response (CR) was achieved with cetuximab alone. Planned treatment duration was 16 weeks (primary endpoint) with the possibility to prolong treatment in case of stable disease (SD) or response. RESULTS: In total, 15 patients have been enrolled. Seven patients were treated for a minimum of 16 weeks and 5 of those patients received cetuximab for at least 28 weeks. One patient received cetuximab treatment as single agent for more than one year. Thrombocytopenia, hyponatremia and acneiform rash were the most common CTC grade 3 or 4 side effects. Acneiform rash CTC grade 1 occurred in all patients and 3 patients suffered from acneiform rash CTC grade 3. After 16 weeks (primary endpoint) cetuximab in combination with dexamethasone induced 4 responses (3 minimal responses (MR) and 1 partial response (PR)) and achieved stable disease (SD) in 1 patient. Cetuximab as single agent induced SD in 2 patients. This results in an intention-to-treat overall response rate (ORR; CR+PR+MR) of 27% and a clinical benefit rate (at least SD) of 47%. Five of the 15 patients included did not receive the planned 16 weeks of treatment due to progressive disease (PD); three patients stopped treatment due to intolerable side effects. Six patients were treated more than 16 weeks: 1 patient received cetuximab as single agent and had SD more than a year and 5 patients continued treatment with cetuximab and dexamethasone in combination. CONCLUSIONS: Cetuximab is feasible and safe in MM patients. It demonstrated moderate efficacy in highly pre-treated patients, especially in combination with dexamethasone. Due to its unique mode of action and favorable side effect profile, cetuximab should be evaluated as combination partner for established substances such as bortezomib or lenalidomide to increase response rates both in therapy naive and in refractory patients. Disclosures: No relevant conflicts of interest to declare.