IMR Press / FBL / Volume 19 / Issue 1 / DOI: 10.2741/4202

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.

Open Access Review

Lorvotuzumab mertansine: antibody-drug-conjugate for CD56+ multiple myeloma

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1 Multiple Myeloma Research, Sarah Cannon Research Institute, Tennessee Oncology, Nashville, TN, USA
Academic Editor:Arthur E. Frankel
Front. Biosci. (Landmark Ed) 2014, 19(1), 163–170; https://doi.org/10.2741/4202
Published: 1 January 2014
(This article belongs to the Special Issue Clinical antibody drug conjugates)
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.

Keywords
Antibody-drug-conjugate
CD56
Multiple myeloma
Lorvotuzumab mertansine
DM1
Review
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