Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
Lorvotuzumab mertansine: antibody-drug-conjugate for CD56+ multiple myeloma
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.