Faculty Collaboration Database

Phase I/II study of the novel proteasome inhibitor delanzomib (CEP-18770) for relapsed and refractory multiple myeloma. Leuk Lymphoma 2017 Aug;58(8):1872-1879

Date

02/01/2017

Pubmed ID

28140719

DOI

10.1080/10428194.2016.1263842

Scopus ID

2-s2.0-85011266750 (requires institutional sign-in at Scopus site)   49 Citations

Abstract

Delanzomib (CEP-18770), a reversible P2 threonine boronic acid proteasome (β5/β1 subunits) inhibitor that showed promising anti-myeloma effects in preclinical studies, was investigated in a single-agent multicenter phase I/II study in patients with relapsed/refractory myeloma. Sixty-one patients (17 during dose escalation; 44 in the expansion cohort) received delanzomib on days 1, 8, and 15 in 28-d cycles; 47 received the maximum tolerated dose (MTD), 2.1 mg/m². Dose-limiting toxicities (DLTs) at 2.4 mg/m² were rash and thrombocytopenia. At the MTD, the most prominent adverse events were nausea, vomiting, anorexia, fatigue, and pyrexia; grade 3/4 thrombocytopenia and neutropenia occurred in 53 and 23% of patients, respectively. Peripheral neuropathy (21%) was limited to grades 1/2. At the MTD, 26 patients (55%) had stable disease and four (9%) had a partial response (PR). Median time to progression (TTP) was 2.5 months across the cohort. Based upon the efficacy results, development of delanzomib for myeloma was discontinued.

Author List

Vogl DT, Martin TG, Vij R, Hari P, Mikhael JR, Siegel D, Wu KL, Delforge M, Gasparetto C

Author

Parameswaran Hari MD Adjunct Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Boronic Acids
Drug Resistance, Neoplasm
Female
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Multiple Myeloma
Proteasome Inhibitors
Recurrence
Retreatment
Threonine
Treatment Outcome