Sikander Ailawadhi1, Kevin R Kelly2, Robert A Vescio3, Sundar Jagannath4, Jeffrey Wolf5, Mecide Gharibo6, Taimur Sher7, Leyla Bojanini7, Maurice Kirby8, Asher Chanan-Khan7. 1. Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL. Electronic address: ailawadhi.sikander@mayo.edu. 2. Division of Hematology/Oncology, University of Southern California Norris Cancer Center, Los Angeles, CA. 3. Multiple Myeloma and Amyloidosis Program, Cedars-Sinai Medical Center, Los Angeles, CA. 4. Division of Hematology and Medical Oncology, Mt. Sinai Medical Center, New York, NY. 5. Myeloma Program, Department of Medicine, University of California San Francisco, San Francisco, CA. 6. Department of Pathology and Laboratory medicine, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ. 7. Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL. 8. Immunogen Inc, Boston, MA.
Abstract
BACKGROUND: Despite therapeutic advancements that have significantly improved outcomes in multiple myeloma (MM), it remains an incurable disease. Patients with relapsed and/or refractory MM have an aggressive disease course, with inferior outcomes, necessitating the need for agents with novel therapeutic mechanisms. We present the results of a completed phase I trial of single-agent lorvotuzumab mertansine, a unique antibody-drug conjugate targeting CD56, which is frequently expressed in MM. PATIENTS AND METHODS: Thirty-seven patients with relapsed MM were enrolled in a dose-escalation phase I clinical trial to determine the maximum tolerated dose of lorvotuzumab mertansine (112 mg/m2), followed by an expansion phase at the maximum tolerated dose. RESULTS: Despite a high proportion of patients with relapsed and/or refractory MM (56.8%), stable disease or better was noted in 42.9% of patients, and these patients had a long duration of response (median, 15.5 months). The adverse event profile was favorable, with a low incidence of grade 3/4 adverse events and no infusion-related reactions. No humoral responses were detected against the study drug. CONCLUSION: This completed phase I trial of single-agent lorvotuzumab mertansine provides ample evidence of safety and signals of clinical activity for this agent, warranting its further clinical development as part of combination regimens for the management of MM.
BACKGROUND: Despite therapeutic advancements that have significantly improved outcomes in multiple myeloma (MM), it remains an incurable disease. Patients with relapsed and/or refractory MM have an aggressive disease course, with inferior outcomes, necessitating the need for agents with novel therapeutic mechanisms. We present the results of a completed phase I trial of single-agent lorvotuzumab mertansine, a unique antibody-drug conjugate targeting CD56, which is frequently expressed in MM. PATIENTS AND METHODS: Thirty-seven patients with relapsed MM were enrolled in a dose-escalation phase I clinical trial to determine the maximum tolerated dose of lorvotuzumab mertansine (112 mg/m2), followed by an expansion phase at the maximum tolerated dose. RESULTS: Despite a high proportion of patients with relapsed and/or refractory MM (56.8%), stable disease or better was noted in 42.9% of patients, and these patients had a long duration of response (median, 15.5 months). The adverse event profile was favorable, with a low incidence of grade 3/4 adverse events and no infusion-related reactions. No humoral responses were detected against the study drug. CONCLUSION: This completed phase I trial of single-agent lorvotuzumab mertansine provides ample evidence of safety and signals of clinical activity for this agent, warranting its further clinical development as part of combination regimens for the management of MM.
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