title: Lorvotuzumab mertansine: antibody-drug-conjugate for CD56+ multiple myeloma.
abstract: Lorvotuzumab mertansine (LM) is an ADC composed of an anti CD56 humanized N901 monoclonal antibody conjugated via a stable disulfide linker to the maytansinoid DM1. CD56 is expressed in up to 78% of multiple myelomas. LM displays antitumor activity in preclinical models of multiple myeloma. In a phase I study of MM, the MTD of single-agent LM was 112 mg/m². The dose-limiting toxicities were grade 3 fatigue and grade 3 acute, reversible, renal failure. 2 PRs and 4 MRs were observed at various dose levels starting at 60 mg/m². Building on the single agent experience, a phase II study of LM in combination with lenalidomide and dexamethasone was conducted. The optimal dose of LM was 75 mg/m² in the combination. The ORR was 56.4%. The most common treatment-related AE was peripheral neuropathy (PN), mostly grade 2 or less, with the majority of patients having a grade 1 PN at baseline. Continued evaluation of optimal dosing levels and schedules will be important to better define the utility of this promising treatment.
authors.affiliation: Multiple Myeloma Research, Sarah Cannon Research Institute, Tennessee Oncology, Nashville, TN, USA.
authors.forename: Jesus G
authors.initials: JG
authors.lastname: Berdeja
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D019002:CD56 Antigen / Q000276:immunology*; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000627:therapeutic use*; D008453:Maytansine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal; D019002:CD56 Antigen; D018796:Immunoconjugates; C579429:lorvotuzumab mertansine; D008453:Maytansine