Phase 1 Study of Tabalumab, a Human Anti-B-Cell Activating Factor Antibody, and Bortezomib in Patients with Relapsed/Refractory Multiple Myeloma.

Autor:	Raje NS; Massachusetts General Hospital, Boston, Massachusetts. NRAJE@mgh.harvard.edu., Faber EA Jr; University of Nebraska Medical Center, Omaha, Nebraska., Richardson PG; Dana Farber Cancer Institute, Boston, Massachusetts., Schiller G; David Geffen School of Medicine at UCLA, Los Angeles, California., Hohl RJ; University of Iowa Hospitals and Clinics, Iowa City, Iowa., Cohen AD; Fox Chase Cancer Center, Philadelphia, Pennsylvania., Forero A; University of Alabama at Birmingham, Birmingham, Alabama., Carpenter S; Eli Lilly and Company, Indianapolis, Indiana., Nguyen TS; Eli Lilly and Company, Indianapolis, Indiana., Conti I; Eli Lilly and Company, Indianapolis, Indiana., Kaiser CJ; Eli Lilly and Company, Indianapolis, Indiana., Cronier DM; Eli Lilly and Company, Indianapolis, Indiana., Wooldridge JE; Eli Lilly and Company, Indianapolis, Indiana., Anderson KC; Dana Farber Cancer Institute, Boston, Massachusetts.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2016 Dec 01; Vol. 22 (23), pp. 5688-5695. Date of Electronic Publication: 2016 Jun 10.
DOI:	10.1158/1078-0432.CCR-16-0201
Abstrakt:	Purpose: Tabalumab, a human mAb that neutralizes B-cell-activating factor (BAFF), demonstrated antitumor activity in xenograft models of multiple myeloma. Here we report on a phase I study of relapsed/refractory multiple myeloma patients in which the primary objective was to identify a tolerable and potentially efficacious dose of tabalumab when combined with bortezomib. Experimental Design: Forty-eight patients were enrolled; 20 to the dose-escalation cohort, and 28 to cohort expansion in which a dose of 100 mg of tabalumab was evaluated. All patients had received either prior bortezomib or an immunomodulatory drug; the median number of prior therapies was 3. Bortezomib was administered intravenously on days 1, 4, 8, and 11 of a 21-day schedule. Tabalumab was given every 21 days for 3 cycles, then every 42 days thereafter. Results: The most common grade 3/4 toxicities included thrombocytopenia, neutropenia, pneumonia, and peripheral sensory neuropathy. There were no dose-limiting toxicities, and the maximum tolerated dose was not reached. Pharmacokinetic data suggested serum exposure increased in a greater than dose-proportional manner up to a dose of 100 mg. Out of 46 evaluable patients, 20 had confirmed responses. The median time to progression (9 patients censored) was 4.8 months, and the median response duration (4 patients censored) was 7.2 months. Conclusions: A dose of 100 mg tabalumab in combination with bortezomib was well tolerated and active and is currently under further investigation. Clin Cancer Res; 22(23); 5688-95. ©2016 AACR. (©2016 American Association for Cancer Research.)
Databáze:	MEDLINE
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