Phase 2 study of dovitinib in patients with relapsed or refractory multiple myeloma with or without t(4;14) translocation

Christof Scheid, Donna Reece, Meral Beksac, Andrew Spencer, Natalie Callander, Pieter Sonneveld, Ghulam Kalimi, Can Cai, Michael Shi, Jeffrey W. Scott, Alexander Keith Stewart

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Objectives: Approximately 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. Methods: Adult 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 (500 mg/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. Results: In total, 43 patients (median age, 63 years) 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 8.7 weeks in the t(4;14)-positive group and 3.7 weeks 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%). Conclusion: Dovitinib showed no single-agent activity in relapsed or refractory MM but may stabilize disease in some t(4;14)-positive patients.

Original languageEnglish (US)
Pages (from-to)316-324
Number of pages9
JournalEuropean Journal of Haematology
Volume95
Issue number4
DOIs
StatePublished - Oct 1 2015

Fingerprint

Multiple Myeloma
Receptor Protein-Tyrosine Kinases
Receptor, Fibroblast Growth Factor, Type 3
4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one
Nausea
Dexamethasone
Vomiting
Fatigue
Diarrhea
Appointments and Schedules
Research Personnel
Safety
Therapeutics

Keywords

  • Dovitinib
  • FGFR3
  • Phase 2
  • Relapsed or refractory multiple myeloma
  • T(4;14) translocation

ASJC Scopus subject areas

  • Hematology

Cite this

Phase 2 study of dovitinib in patients with relapsed or refractory multiple myeloma with or without t(4;14) translocation. / Scheid, Christof; Reece, Donna; Beksac, Meral; Spencer, Andrew; Callander, Natalie; Sonneveld, Pieter; Kalimi, Ghulam; Cai, Can; Shi, Michael; Scott, Jeffrey W.; Stewart, Alexander Keith.

In: European Journal of Haematology, Vol. 95, No. 4, 01.10.2015, p. 316-324.

Research output: Contribution to journalArticle

Scheid, C, Reece, D, Beksac, M, Spencer, A, Callander, N, Sonneveld, P, Kalimi, G, Cai, C, Shi, M, Scott, JW & Stewart, AK 2015, 'Phase 2 study of dovitinib in patients with relapsed or refractory multiple myeloma with or without t(4;14) translocation', European Journal of Haematology, vol. 95, no. 4, pp. 316-324. https://doi.org/10.1111/ejh.12491
Scheid, Christof ; Reece, Donna ; Beksac, Meral ; Spencer, Andrew ; Callander, Natalie ; Sonneveld, Pieter ; Kalimi, Ghulam ; Cai, Can ; Shi, Michael ; Scott, Jeffrey W. ; Stewart, Alexander Keith. / Phase 2 study of dovitinib in patients with relapsed or refractory multiple myeloma with or without t(4;14) translocation. In: European Journal of Haematology. 2015 ; Vol. 95, No. 4. pp. 316-324.
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abstract = "Objectives: Approximately 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. Methods: Adult 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 (500 mg/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. Results: In total, 43 patients (median age, 63 years) 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 8.7 weeks in the t(4;14)-positive group and 3.7 weeks 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{\%}). Conclusion: Dovitinib showed no single-agent activity in relapsed or refractory MM but may stabilize disease in some t(4;14)-positive patients.",
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AU - Spencer, Andrew

AU - Callander, Natalie

AU - Sonneveld, Pieter

AU - Kalimi, Ghulam

AU - Cai, Can

AU - Shi, Michael

AU - Scott, Jeffrey W.

AU - Stewart, Alexander Keith

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