J Clin Oncol 31, 2013 (suppl; abstr 8542)
Sagar Lonial, Sundar Jagannath, Philippe Moreau, Andrzej J. Jakubowiak, Marc S. Raab, Thierry Facon, Ravi Vij, Eric Bleickardt, Donna Ellen Reece, Lotfi Benboubker, Jeffrey A. Zonder, Wei Deng, Anil K. Singhal, Paul Gerard Guy Richardson, on behalf of the 1703 Study Investigators; Emory University School of Medicine, Atlanta, GA; Multiple Myeloma Research Consortium, Norwalk, CT/Mount Sinai Medical Center, New York, NY; Hematology, University Hospital Hotel-Dieu, Nantes, France; Multiple Myeloma Research Consortium, Norwalk, CT/University of Chicago, Chicago, IL; Universitaetsklinikum Heidelberg, Heidelberg, Germany; Hôpital Claude Huriez, Lille, France; Multiple Myeloma Research Consortium, Norwalk, CT/Washington University School of Medicine, St. Louis, MO; Bristol-Myers Squibb, Wallingford, CT; Princess Margaret Hospital, Toronto, ON, Canada; Centre Hospitalier Universitaire Tours-Hopital Bretonneau, Tours, France; Multiple Myeloma Research Consortium, Norwalk, CT/Karmanos Cancer Institute, Detroit, MI; AbbVie Biotherapeutics Incorporated, Redwood City, CA; AbbVie Biotherapeutics Corporation, Redwood City, CA; Multiple Myeloma Research Consortium, Norwalk, CT/Dana-Farber Cancer Institute, Boston, MA
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.