Phase I Trial of Anti-CS1 Monoclonal Antibody Elotuzumab in Combination With Bortezomib in the Treatment of Relapsed/Refractory Multiple Myeloma

University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
Journal of Clinical Oncology (Impact Factor: 18.43). 01/2012; 30(16):1960-5. DOI: 10.1200/JCO.2011.37.7069
Source: PubMed


To evaluate the maximum-tolerated dose (MTD), safety, and efficacy of elotuzumab in combination with bortezomib in patients with relapsed or relapsed and refractory multiple myeloma (MM).
Elotuzumab (2.5, 5.0, 10, or 20 mg/kg intravenously [IV]) and bortezomib (1.3 mg/m(2) IV) were administered on days 1 and 11 and days 1, 4, 8, and 11, respectively, in 21-day cycles by using a 3 + 3 dose-escalation design. Patients with stable disease or better after four cycles could continue treatment until disease progression or unexpected toxicity. Responses were assessed during each cycle by using European Group for Blood and Marrow Transplantation (EBMT) criteria.
Twenty-eight patients with a median of two prior therapies were enrolled; three patients each received 2.5, 5.0, and 10 mg/kg of elotuzumab and 19 received 20 mg/kg (six during dose escalation and 13 during an expansion phase). No dose-limiting toxicities were observed during cycle 1 of the dose-escalation phase, and the MTD was not reached up to the maximum planned dose of 20 mg/kg. The most frequent grade 3 to 4 adverse events (AEs) were lymphopenia (25%) and fatigue (14%). Two elotuzumab-related serious AEs of chest pain and gastroenteritis occurred in one patient. An objective response (a partial response or better) was observed in 13 (48%) of 27 evaluable patients and in two (67%) of three patients refractory to bortezomib. Median time to progression was 9.46 months.
The combination of elotuzumab and bortezomib was generally well-tolerated and showed encouraging activity in patients with relapsed/refractory MM.

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    • "ELO is a humanized monoclonal IgG1 antibody that targets CS-1, a cell surface glycoprotein with dense expression in malignant plasma cells. Targeting CS-1 has been shown to lead to natural killer (NK)-cell mediated antibody dependent cellular cytotoxicity (ADCC).17,19 Clinical trials have combined ELO with lenalidomide (LEN) and dexamethasone (DEX) in patients with relapsed myeloma. "
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    OncoTargets and Therapy 06/2014; 7:1095-100. DOI:10.2147/OTT.S49480 · 2.31 Impact Factor
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    • "The most frequent grades 3 to 4 adverse events were lymphopenia and fatigue. Two elotuzumab-related serious adverse events (chest pain and gastroenteritis) occurred in one patient [57]. "
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    BioMed Research International 05/2014; 2014:456037. DOI:10.1155/2014/456037 · 2.71 Impact Factor
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    • "Normal plasma cells express high levels of CS1, which correlates with high expression on MM cells (60). CS1 is an attractive therapeutic ADCC target because the available clinical data indicate that expression persists on MM cells even after conventional treatments (61–63). CS1 was originally found to engage in homotypic interactions as a self-ligand, and pretreatment of a NK cell line with recombinant CS1-Ig fusion protein was shown to stimulate killing of K562 target cells, apparently by directly activating the NK cells via homotypic interaction (64). "
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