Elotuzumab is a monoclonal antibody that specifically targets Signaling Lymphocytic Activation Molecule F7 (SLAMF7), a protein expressed on myeloma and natural killer cells, to induce both immunostimulatory and direct antimyeloma cytotoxic effects. Based on preclinical evidence of enhanced antimyeloma activity when combined with a proteasome inhibitor, a phase 2 study (CA204-009T) compared the efficacy and safety of elotuzumab plus bortezomib and dexamethasone (EBd) versus bortezomib and dexamethasone (Bd) alone in patients with relapsed/refractory multiple myeloma (RRMM).1,2 One-year results of the trial demonstrated that EBd therapy significantly prolonged progression-free survival (PFS) compared with Bd (9.7 vs 6.9 months; hazard ratio [HR], 0.72; P = .09) in this patient population. Palumbo and colleagues reported on 2-year updated efficacy and safety results of the CA204-009T trial at the 2015 ASH meeting.3
In this trial, 152 eligible patients with RRMM who had failed 1 to 3 prior therapies were treated with EBd (n = 77; elotuzumab 10 mg/kg intravenously; bortezomib 1.3 mg/m2 intravenously/subcutaneously; dexamethasone 20 mg orally) or Bd (n = 75) until disease progression or unacceptable toxicity. Dexamethasone 20 mg was administered on days when elotuzumab was not administered.
In terms of efficacy, EBd treatment was associated with a significant prolongation of PFS compared with Bd treatment, with a 24% reduction in the risk of disease progression and a 25% reduction in the risk of death (HR, 0.75; P = .09); the median PFS was 9.7 months vs 6.9 months with EBd vs Bd, respectively. The 2-year PFS rate was 18% with EBd therapy compared with 11% with Bd therapy; overall response rates were similar between the 2 arms. The superiority in PFS of EBd over Bd was observed across all prespecified subgroups, including age, ISS stage at enrollment, number of lines of prior therapy, prior proteasome inhibitor use, and prior immunomodulatory therapy. Moreover, investigation of FCΥRIIIa receptor polymorphism on natural killer (NK) cells to which the Fc portion of elotuzumab binds revealed a low affinity (FF) allele and a high affinity (VV) allele; median PFS was 22.3 months in the EBd/VV group compared with 9.8 months in the EBd/FF group, suggesting a trend toward longer PFS in EBd-treated patients that are homozygous for the high affinity FCΥRIIIa V allele. Grade 3/4 adverse events were reported in 71% of the patients in the EBd arm and 60% of those in the Bd arm, including thrombocytopenia and infections. Study drug discontinuation was mainly due to disease progression (56% across treatment arms). Based on these long-term data, the authors concluded that elotuzumab combined with bortezomib and dexamethasone demonstrated significant and durable improvements in progression-free survival. The safety profile of EBd was comparable to Bd alone.
- Jakubowiak A, et al. J Clin Oncol. 2012;30:1960-1965.
- Jakubowiak A, et al. ASCO 2015. Abstract 8573.
- Palumbo A, et al. ASH 2015. Abstract 510.