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Clinical Trial
. 2014 Feb;92(2):127-36.
doi: 10.1111/ejh.12210. Epub 2013 Nov 25.

Characterization of different regimens for initiating anagrelide in patients with essential thrombocythemia who are intolerant or refractory to their current cytoreductive therapy: results from the multicenter FOX study of 177 patients in France

Jérôme Rey  1 , Jean-François Viallard, Karim Keddad, Jonathan Smith, Paul Wilde, Jean-Jacques Kiladjian; FOX study investigators
Collaborators, Affiliations
Clinical Trial

Characterization of different regimens for initiating anagrelide in patients with essential thrombocythemia who are intolerant or refractory to their current cytoreductive therapy: results from the multicenter FOX study of 177 patients in France

Jérôme Rey et al. Eur J Haematol. 2014 Feb.

Abstract

Objectives: To identify switch modalities used when initiating second- or third-line anagrelide for essential thrombocythemia (ET), assess whether anagrelide is initiated consistently with Summary of Product Characteristics (SPC) recommendations, and determine whether different observed switch regimens have any relationship with maintenance, platelet response, or tolerability.

Methods: This observational study was conducted across 43 centers in France. High-risk patients (>60 yr of age and/or history of thrombosis and/or platelet count >1000 × 10(9) /L) with ET starting second- or third-line anagrelide therapy were identified and monitored for 6 months.

Results: A total of 177 patients were enrolled. The SPC-recommended starting dose (1 mg/d) was used in 52.6% of patients; 0.5 mg/d was used in 41.1%. 77.1% of patients underwent an anagrelide dose increase during the study. At 6-month follow-up, 84.7% of patients (n = 144/170) were still receiving anagrelide; 70.6% (n = 120/170) achieved a platelet response. A higher proportion of patients who discontinued previous cytoreductive therapy (CRT) after initiating anagrelide achieved a platelet response (n = 34/39, 87.2%) vs. patients who discontinued their previous CRT before anagrelide initiation (n = 77/115, 67.0%). Platelet response rates were higher in patients whose anagrelide initiation was consistent (n = 100/133, 75.2%) vs. inconsistent (n = 20/37, 54.1%) with the SPC. The incidence of adverse drug reactions was lower in patients whose anagrelide treatment was consistent (n = 52/133, 39.1%) vs. inconsistent (n = 25/37, 67.6%) with the SPC.

Conclusions: To our knowledge, the FOX study provides the first comprehensive real-world data on the modalities used when switching from previous CRT to anagrelide. Highest platelet responses were observed when previous CRT was discontinued after anagrelide initiation or when anagrelide was initiated consistently with the SPC. Safety data corresponded with the SPC.

Trial registration: ClinicalTrials.gov NCT01192347.

Keywords: anagrelide; blood platelets; essential thrombocythemia; hydroxycarbamide; intolerance; myeloproliferative disorders; platelet count; resistance; switch.

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Figures

Figure 1
Figure 1
Patient disposition. ANA, anagrelide; CRT, cytoreductive therapy; SPC, Summary of Product Characteristics. 0–1 month: CRT was discontinued within the first 30 d of anagrelide treatment (median 10 d). 1–6 months: CRT was continued for ≥30 d (median 65 d), but was discontinued before anagrelide was discontinued or the patient completed the study period. Not discontinued: all other cases (i.e., patients received both their current CRT and anagrelide throughout the 6-month follow-up period). 1Includes two patients who restarted CRT after anagrelide initiation that was discontinued again in the 6-month follow-up period.
Figure 2
Figure 2
Proportion of patients continuing anagrelide treatment at 6 months: full analysis set. ANA, anagrelide; CRT, cytoreductive therapy; SPC, Summary of Product Characteristics.
Figure 3
Figure 3
Platelet responses by main subgroups: full analysis set. ANA, anagrelide; CRT, cytoreductive therapy; SPC, Summary of Product Characteristics.
See this image and copyright information in PMC

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