Blood Res.  2018 Jun;53(2):123-129. 10.5045/br.2018.53.2.123.

Effectiveness of darbepoetin alfa in multiple myeloma patients receiving chemotherapy including novel agents

• Lee SE
• Jeon YW
• Yoon JH
• Cho BS
• Eom KS
• Kim YJ
• Kim HJ
• Lee S
• Cho SG
• Kim DW
• Lee JW
• Min WS
• Min CK

• KMID: 2451030
• DOI: http://doi.org/10.5045/br.2018.53.2.123

Abstract

BACKGROUND
The aim of this study was to evaluate the effects of darbepoetin alfa (DA) on hemoglobin (Hb) concentration and the need for transfusions in multiple myeloma (MM) patients receiving chemotherapy with novel agents.
METHODS
Of 251 patients with MM who received DA therapy for at least 4 weeks, 142 who did not receive RBC transfusion during 4 weeks after DA initiation and started DA therapy at baseline Hb <10.0 g/dL were analyzed.
RESULTS
After 4 weeks of DA therapy, 80 (60.6%) of 132 patients with evaluable data had Hb that increased ≥1.0 g/dL from baseline, while 50 (37.9%) had Hb that increased ≥2.0 g/dL from baseline. Pretreatment Hb level did not correlate with the proportion of patients with increased Hb. The median duration of DA therapy was 9.0 weeks. At the end of DA therapy, of 135 patients with evaluable data, 86 (60.6%) had Hb that increased ≥1.0 g/dL from baseline, while 67 (47.2%) had Hb that increased ≥2.0 g/dL from baseline. Stage III disease according to the International Staging System and absence of myeloma bone disease at diagnosis were independent predictors of higher Hb response during early DA therapy.
CONCLUSION
We demonstrated the efficacy of DA therapy in a homogeneous group of MM patients receiving chemotherapy. DA therapy significantly increased Hb concentration, regardless of baseline Hb level.

Keyword

Multiple myeloma; Anemia; Erythropoietin

MeSH Terms

Anemia
Bone Diseases
Darbepoetin alfa*
Diagnosis
Drug Therapy*
Erythropoietin
Humans
Multiple Myeloma*
Darbepoetin alfa
Erythropoietin

Figure

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  Fig. 1 Cumulative incidences of Hb response (≥2.0 g/dL).

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  Fig. 2 Mean (SEM) change in hemoglobin during darbepoetin alfa therapy. (A) Mean (SEM) changes in hemoglobin from baseline to 4 weeks and (B) to the end of darbepoetin alfa therapy.

Reference

1. Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003; 78:21–33. PMID: 12528874.

2. Birgegård G, Gascón P, Ludwig H. Evaluation of anaemia in patients with multiple myeloma and lymphoma: findings of the European Cancer Anaemia Survey. Eur J Haematol. 2006; 77:378–386. PMID: 17044835.

3. Ludwig H, Strasser K. Symptomatology of anemia. Semin Oncol. 2001; 28(2 Suppl 8):7–14.

4. Cella D. Factors influencing quality of life in cancer patients: anemia and fatigue. Semin Oncol. 1998; 25(3 Suppl 7):43–46.

5. Ludwig H, Van Belle S, Barrett-Lee P, et al. The European Cancer Anaemia Survey (ECAS): A large, multinational, prospective survey defining the prevalence, incidence, and treatment of anaemia in cancer patients. Eur J Cancer. 2004; 40:2293–2306. PMID: 15454256.

6. Ludwig H, Miguel JS, Dimopoulos MA, et al. International Myeloma Working Group recommendations for global myeloma care. Leukemia. 2014; 28:981–992. PMID: 24177258.

7. Lundin AP, Delano BG, Quinn-Cefaro R. Perspectives on the improvement of quality of life with epoetin alfa therapy. Pharmacotherapy. 1990; 10:22S–26S. PMID: 2345708.

8. Scott SD. Dose conversion from recombinant human erythropoietin to darbepoetin alfa: recommendations from clinical studies. Pharmacotherapy. 2002; 22:160S–165S. PMID: 12222586.

9. Hedenus M, Hansen S, Taylor K, et al. Randomized, dose-finding study of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies. Br J Haematol. 2002; 119:79–86. PMID: 12358906.

10. Pirker R, Hedenus M, Vansteenkiste J, Hernandez E, Belton L, Terwey JH. Effectiveness of darbepoetin alfa for chemotherapy-induced anemia when initiated at hemoglobin ≤10 g/dL. Clin Ther. 2016; 38:122–135.e6. PMID: 26730453.

11. Grossi A, Balestri F, Santini S. Darbepoetin alpha in the treatment of cancer chemotherapy-induced anemia. Ther Clin Risk Manag. 2007; 3:269–275. PMID: 18360635.

12. Hedenus M, Adriansson M, San Miguel J, et al. Efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies: a randomized, double-blind, placebo-controlled study. Br J Haematol. 2003; 122:394–403. PMID: 12877666.

13. Musto P, Lanza F, Balleari E, et al. Darbepoetin alpha for the treatment of anaemia in low-intermediate risk myelodysplastic syndromes. Br J Haematol. 2005; 128:204–209. PMID: 15638854.

14. Patton JF, Sullivan T, Mun Y, Reeves T, Rossi G, Wallace JF. A retrospective cohort study to assess the impact of therapeutic substitution of darbepoetin alfa for epoetin alfa in anemic patients with myelodysplastic syndrome. J Support Oncol. 2005; 3:419–426. PMID: 16350429.

15. Osterborg A, Boogaerts MA, Cimino R, et al. Recombinant human erythropoietin in transfusion-dependent anemic patients with multiple myeloma and non-Hodgkin's lymphoma--a randomized multicenter study. The European Study Group of Erythropoietin (Epoetin Beta) Treatment in Multiple Myeloma and Non-Hodgkin's Lymphoma. Blood. 1996; 87:2675–2682. PMID: 8639883.

16. Dammacco F, Castoldi G, Rödjer S. Efficacy of epoetin alfa in the treatment of anaemia of multiple myeloma. Br J Haematol. 2001; 113:172–179. PMID: 11328297.

17. Littlewood TJ, Zagari M, Pallister C, Perkins A. Baseline and early treatment factors are not clinically useful for predicting individual response to erythropoietin in anemic cancer patients. Oncologist. 2003; 8:99–107. PMID: 12604736.

18. Beguin Y, Yerna M, Loo M, Weber M, Fillet G. Erythropoiesis in multiple myeloma: defective red cell production due to inappropriate erythropoietin production. Br J Haematol. 1992; 82:648–653. PMID: 1482651.

19. Mittelman M, Neumann D, Peled A, Kanter P, Haran-Ghera N. Erythropoietin induces tumor regression and antitumor immune responses in murine myeloma models. Proc Natl Acad Sci U S A. 2001; 98:5181–5186. PMID: 11309490.

20. Bohlius J, Wilson J, Seidenfeld J, et al. Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. J Natl Cancer Inst. 2006; 98:708–714. PMID: 16705125.