Universität zu Köln

Scheid, Christof, Reece, Donna, Beksac, Meral, Spencer, Andrew, Callander, Natalie ORCID: 0000-0002-6975-1086, Sonneveld, Pieter, Kalimi, Ghulam, Cai, Can, Shi, Michael, Scott, Jeffrey W. and Stewart, A. Keith (2015). Phase 2 study of dovitinib in patients with relapsed or refractory multiple myeloma with or without t(4;14) translocation. Eur. J. Haematol., 95 (4). S. 316 - 325. HOBOKEN: WILEY. ISSN 1600-0609

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Abstract

ObjectivesApproximately 15% of patients with multiple myeloma (MM) exhibit a t(4;14) translocation, which often results in constitutive activation of the receptor tyrosine kinase (RTK) fibroblast growth factor receptor 3 (FGFR3). This study evaluated the efficacy and safety of dovitinib, an RTK inhibitor with in vitro inhibitory activity against FGFR, in patients with relapsed or refractory MM with or without t(4;14) translocation. MethodsAdult patients with relapsed or refractory MM who had received 2 prior regimens were enrolled in this multicenter, 2-stage, phase 2 trial. Patients were grouped based on their t(4;14) status. Dovitinib (500mg/day orally) was administered on a 5-days-on/2-days-off schedule. The primary endpoint was overall response rate by local investigator review (per International Myeloma Working Group criteria). In non-responding patients, treatment could continue with the addition of low-dose dexamethasone. ResultsIn total, 43 patients (median age, 63years) were enrolled (13 t(4;14) positive, 26 t(4;14) negative, and 4 t(4;14) status non-interpretable). Patients had received a median of 5 prior regimens. Median duration of treatment was 8.7weeks in the t(4;14)-positive group and 3.7weeks in the t(4;14)-negative group. None of the patients on dovitinib had objective responses. The stable disease rate was 61.5% in the t(4;14)-positive group and 34.6% in the t(4;14)-negative group. Overall, 39 patients (90.7%) had adverse events suspected to be related to study drug, most commonly diarrhea (60.5%), nausea (58.1%), vomiting (46.5%), and fatigue (32.6%). ConclusionDovitinib showed no single-agent activity in relapsed or refractory MM but may stabilize disease in some t(4;14)-positive patients.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Scheid, Christof UNSPECIFIED UNSPECIFIED UNSPECIFIED Reece, Donna UNSPECIFIED UNSPECIFIED UNSPECIFIED Beksac, Meral UNSPECIFIED UNSPECIFIED UNSPECIFIED Spencer, Andrew UNSPECIFIED UNSPECIFIED UNSPECIFIED Callander, Natalie UNSPECIFIED orcid.org/0000-0002-6975-1086 UNSPECIFIED Sonneveld, Pieter UNSPECIFIED UNSPECIFIED UNSPECIFIED Kalimi, Ghulam UNSPECIFIED UNSPECIFIED UNSPECIFIED Cai, Can UNSPECIFIED UNSPECIFIED UNSPECIFIED Shi, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Scott, Jeffrey W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stewart, A. Keith UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-391759
DOI:	10.1111/ejh.12491
Journal or Publication Title:	Eur. J. Haematol.
Volume:	95
Number:	4
Page Range:	S. 316 - 325
Date:	2015
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1600-0609
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GROWTH-FACTOR RECEPTOR-3; KINASE INHIBITOR; STAT ACTIVATION; FGFR3; IDENTIFICATION; CHIR-258; EXPRESSION; PROGNOSIS; THERAPY; PATHWAY Multiple languages Hematology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/39175