Background: ESA have been reported to effectively improve the hemoglobin (Hb) in pts with CML who develop anemia during the course of therapy with imatinib and other tyrosine kinase inhibitors. Recently, it has been suggested that when ESA were administered to target a Hb ≥12 g/dL, they may promote tumor growth and decreased survival among pts with advanced head and neck cancer receiving radiation therapy, pts with non-small cell lung cancer, and pts with metastatic breast cancer receiving chemotherapy. We thus investigated whether pts with CML who had received ESA during the course of therapy with imatinib had an inferior long-term outcome.

Methods: We analyzed the outcome of 565 pts with CML in chronic phase treated with imatinib in our institution (306 previously untreated, 259 post imatinib failure).

Results: Based on the Common Terminology Criteria for Adverse Events (CTCAE) V. 3.0 of the National Cancer Institute (NCI), grade 1 anemia occurred in 235 (42%) pts, grade 2 in 180 (32%), grade 3 in 47 (8%), and grade 4 in 12 (2%) pts. A total of 245 (43%) pts received ESA at some point during the course of therapy. The median nadir Hb among pts treated with ESA was 9.4 g/dL [45 (18%) with grade 3–4 anemia] vs 11.2 g/dL [14 (4%) with grade 3–4 anemia] in those not treated with ESA. Treated patients received therapy with variable intermittent doses during a median time of 14 months (mo) range (1–96 mo). The observed increase in Hb with ESA therapy was >3 g/dL in 132 (54%) pts, 2–3 g/dL in 64 (26%), 1-<2 g/dL in 35 (14%), and <1 g/dL in 14 (6%) pts. The median Hb level achieved with ESA was 12.6 g/dL. The table summarizes the 5-year overall survival and event free survival (EFS) among pts treated with ESA and those not treated with ESA: As previously reported (

Cortes et al. Cancer 2004; 100:2396–402
), the presence of anemia itself has a significant adverse effect on outcome in this patient population. The 5-year EFS for pts with anemia grade 3–4 was 56% vs. 79% for those with grade 0–2 (p=0.002). Corresponding figures for 5-yr OS were 82% and 88% (p=0.006).

Conclusion: There is no evidence that the use of ESA to manage anemia associated with imatinib therapy in pts with CML in chronic phase adversely affects long term overall survival or event-free survival.

INF- failure (%)Frontline Imatinib (%)
OS: overall survival, EFS: event free survival (event = loss of complete hematologic response, loss of major cytogenetic response, transformation to accelerated or blast phase or death from any cause), INF: interferon, ESA: erythropoiesis-stimulating agents. 
ESA use OS EFS OS EFS 
No 84 75 92 84 
Yes 82 68 89 85 
P Value 0.59 0.12 0.58 0.68 
INF- failure (%)Frontline Imatinib (%)
OS: overall survival, EFS: event free survival (event = loss of complete hematologic response, loss of major cytogenetic response, transformation to accelerated or blast phase or death from any cause), INF: interferon, ESA: erythropoiesis-stimulating agents. 
ESA use OS EFS OS EFS 
No 84 75 92 84 
Yes 82 68 89 85 
P Value 0.59 0.12 0.58 0.68 

Author notes

Disclosure:Research Funding: JC receives research support from Ortho Biotech. HK receives reasearch support from Amgen. Off Label Use: ESA are not approved for use in CML.

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