Phase (Ph) I/II study of elotuzumab (Elo) plus lenalidomide/dexamethasone (Len/dex) in relapsed/refractory multiple myeloma (RR MM): Updated Ph II results and Ph I/II long-term safety.

8542 Background: Elotuzumab (Elo) is a humanized anti-CS1monoclonal antibody that enhances natural killer cell mediated antibody dependent cellular cytotoxicity of CS1 expressing myeloma cells. This study included a dose finding Ph I cohort (N=28) and a Ph II cohort (N=73). Here we update Ph II data and provide long term safety data from both cohorts. Methods: Patients (pts) treated with ≥1 (Ph I) or 1–3 (Ph II) prior therapies received Elo + Len/dex as described previously (Lonial JCO 2012; Richardson ASH 2012) until disease progression, unacceptable toxicity, or death. All pts received a premedication regimen including methylprednisolone, diphenhydramine or equivalent, ranitidine or equivalent, and acetaminophen to mitigate infusion reactions. Adverse events (AEs) in Ph I/II pts occurring ≤18 months (mo) (N=98) were compared to AEs with a >18 mo onset in a subgroup of pts treated >18 mo (n=49). This safety analysis excluded 3 Ph I pts treated with Elo 5 mg/kg. Results: In the Ph II cohort (median 63 yr), objective response rate (ORR) was 84%; 92% with 10 mg/kg (n=36) and 76% with 20 mg/kg (n=37). At a median follow-up of 20.8 mo, median progression free survival (PFS) was not reached (10 mg/kg) and 18.6 mo (20 mg/kg). Most common treatment emergent grade ≥3 AEs were lymphopenia (19%), neutropenia (18%), thrombocytopenia (16%) and anemia (14%). Most common grade 3/4 AEs emerging ≤18 vs >18 mo in Ph I/II cohorts are shown (Table). 15 pts discontinued due to AEs; none after 18 mo of treatment. There were 4 second primary malignancies; none were reported after 18 mo. Conclusions: Elo 10 mg/kg + Len/dex was generally well tolerated and resulted in a high ORR and encouraging PFS in pts with RR MM. AEs emergent after 18 mo of therapy were consistent with AEs during the initial 18 mo. Updated Ph II safety/efficacy data and long term safety data from Ph I/II cohorts will be presented.