Darbepoetin alfa for anemia in patients with low or intermediate-1 risk myelodysplastic syndromes and positive predictive factors of response

Abstract

Background:

Current guidelines support the use of erythropoiesis-stimulating agents for the treatment of anemia associated with low-risk myelodysplastic syndromes (MDS).

Design and methods:

Single-arm, open-label, multi-center, phase 2 trial that evaluated the efficacy and safety of darbepoetin alfa (DA) in patients with low or intermediate-risk MDS, hemoglobin <100 g/L, erythropoietin (EPO) levels <500 IU/L and transfusion requirements <2 units/month over the preceding 2 months. Erythroid response (major [MaR] or minor [MiR]) and fatigue (Functional Assessment of Cancer Therapy–Fatigue [FACT-F]) were evaluated at 8, 16 and 24 weeks. DA was initiated at 300 μg weekly. For patients who did not achieve MaR by 8 weeks, filgrastim 300 μg weekly was added.

Clinical trial registration:

clinicaltrials.gov identifier: NCT01039350.

Results:

Forty-four patients (72.7% transfusion independent) were included. Median age was 76.0 years (range 41.3–92.4), 54.5% were male, and 90.9% presented ECOG Status (0–1). Eighteen patients received filgrastim. An erythroid response was achieved by 31 of 44 patients (70.5%) at week 8 (47.7% MaR, 22.7% MiR), 31 of 44 patients (70.5%) at week 16 (61.4% MaR, 9.1% MiR), and 32 of 44 patients (72.7%) at week 24 (61.3% MaR, 11.4% MiR). Mean (95% CI) change in FACT-F at week 24 was 3.61 (0.72 to 6.51). Baseline EPO levels <100 IU/L were a predictive factor of response. DA was well tolerated. Four mild (two iron deficiencies, flu syndrome and headache) and one fatal (thromboembolic event) adverse events were considered related to darbepoetin alfa.

Conclusions:

A fixed dose of 300 μg of darbepoetin alfa weekly (with or without filgrastim) seems to be an effective and safe treatment for anemic patients with low or intermediate-risk MDS, low transfusion burden and EPO levels <500 IU/L. Results may not be extrapolable to unselected MDS patients.

Key words::

• Anemia
• Darbepoetin alfa
• Erythroid response
• Fatigue
• Myelodysplastic syndromes

Transparency

Declaration of funding

The sponsor for the study was the Fundación Española de Hematología y Hemoterapia (FEHH). The study was financially supported by Amgen S.A. and by the Fundación Española de Hematología y Hemoterapia (FEHH). The medical writing support was funded by Amgen S.A. Contributorships of authors: A.V. and B.A. designed the study, co-ordinated the group, and wrote the manuscript. J.A.G. reviewed the analysis and the manuscript. The other authors contributed to clinical data collection and reviewed the manuscript.

The CMRO peer reviewers have disclosed that they have no relevant financial relationships.

Declaration of financial/other relationships

A.V. has disclosed that she has no significant relationships with or financial interests in any commercial companies related to this study or article; B.A. has disclosed that she has no significant relationships with or financial interests in any commercial companies related to this study or article; C.F. has disclosed that he has no significant relationships with or financial interests in any commercial companies related to this study or article; M.C. has disclosed that she has no significant relationships with or financial interests in any commercial companies related to this study or article; J.R.M. has disclosed that he has no significant relationships with or financial interests in any commercial companies related to this study or article; J.R.G. has disclosed that he has no significant relationships with or financial interests in any commercial companies related to this study or article; R.F.D. has disclosed that he has no significant relationships with or financial interests in any commercial companies related to this study or article; A.F.R. has disclosed that he has no significant relationships with or financial interests in any commercial companies related to this study or article; E.L. has disclosed that she has no significant relationships with or financial interests in any commercial companies related to this study or article; J.A.G. is an employee of Amgen S.A.

Acknowledgments

This study has been conducted by the above-signed authors and the ARAMYS study group (in alphabetical order): Dra. B. Arrizabalaga (H. de Cruces), Dra. C. Burgaleta (H. Príncipe de Asturias), Dra. M. Castro (C.H.U. Xeral-Cìes), Dr. Rafael F. Duarte (ICO Duran i Reynals), Dr. A. Escudero (H. Gregorio Marañón), Dr. C. Fernández (C.H.U. Juan Canalejo), Dra. I. Fernández (H. Ramón y Cajal), Dra. F. Gilsanz (H. Univ. Doce de Octubre), Dr. J.R. González (H. Univ. Salamanca), Dr. A. Julià Font (H. de Vall D`Hebron), Dra. E. Luño (H. Univ. Central de Asturias), Dr. B. Nomdedeu (H. Clínic), Dr. G. Martín Núnez (H. Virgen del Puerto), Dr. J.R. Mayans (H. Arnau de Vilanova), Dr. J. A. Muñoz (H. Univ. Puerta del Mar), Dr. F. J. de Paz Andrés (H. G. Univ. Alicante), Dra. B. Pérez (H. General Yagüe), Dra. M.L. Pérez (H. Univ. La Fe), Dr. Á.F. Remacha (H. Santa Creu i Sant Pau), Dra. A. M. Villegas (H. Clínico San Carlos).

This study was supported by an educational grant from Amgen, S.A. and from the Fundación Española de Hematología y Hemoterapia (FEHH). The authors would like to thank the contributions of the SEIF-88 staff (Clinical Research Organization) who helped to conduct the study. Writing assistance was supported by Neus Valveny from Trial Form Support.

Previously presented in abstract form at the 50th American Society of Hematology Annual Meeting (San Francisco, CA, December, 6–9 2008): Villegas A, Arrizabalaga B, Fernandez-Iago C et al. Treatment of anemia with darbepoetin alfa in patients with low and intermediate-1 risk myelodysplastic syndromes. Results from the ARAMYS Study. Blood 2008;112:1184, abstract number 3451.

Notes

^*Neupogen is a registered trade name of Amgen Inc., Thousand Oaks, CA, USA.

^†Aranesp is a registered trade name of Amgen Inc., Thousand Oaks, CA, USA.