Anemic Cancer Research Articles

Utilization of Darbepoetin alfa in Relation to Cancer Patients' Hemoglobin Levels.

Background: Prevailing guidelines through 2006 recommended initiating erythropoiesis stimulating agents (ESAs) for chemotherapy-induced anemia (CIA) at hemoglobin (Hb) levels <11 g/dL, maintaining near 12 g/dL, and withholding at >13 g/dL.Objective and Purpose: To determine darbepoetin alfa (DA) administration patterns in cancer patients and selected factors related to such use.Methods: A retrospective ESA administration-level analysis of Varian Medical Systems electronic medical records (EMRs), which includes 122,985 cancer patients across 13 states and 82 physical sites of care. The study period was 1/1/2005 – 11/30/2006. All DA administrations were recorded with the most recent Hb (day of or up to 7 days prior to administration). The proportion of DA administrations at Hb ≥ 12 and Hb ≥ 13 g/dL were the primary outcome measures. Utilization by Hb level was analyzed for all administrations, stratifying by year, gender, and anemia type. The types of anemia assessed were CIA, anemia of cancer (AOC), and myelodysplastic syndrome (MDS).Results: During the 23 month period, there were 33,923 DA administrations associated with Hb results in 5,252 patients. The proportion of all DA administrations given at Hb≥12 was 7.7%, for Hb≥13 g/dL it was 1.1%; proportions for CIA, AOC, and MDS were 8.1 /1.2% (N = 25,638 administrations), 7.5 /1.0% (N = 7,054), and 2.3 /0.2% (N = 1,231) for Hb ≥12 and ≥13 g/dL respectively. The difference across all three indications was statistically significant (P < 0.005) for both Hb thresholds. Overall, the proportion of all DA administrations at Hb ≥12 g/dL and ≥13 g/dL declined from 8.6% to 7.1% (p<.0001) and from 1.3% to 1.0% (p<.06) respectively in 2005 vs. 2006.Conclusions: In this population, DA administration at Hb ≥ 12 and Hb ≥ 13 occurred in approximately 7.7% and 1.1% of administrations, respectively. The results suggest that for the majority of administrations the prevailing guidelines at the time were adhered to by clinicians. Further research is required to understand dose titrations at Hb from 12 – 13 g/dL.

Risk of Adverse Events Is Similar in Patients (Pts) Who Did or Did Not Achieve Hemoglobin (Hb) Above 12g/dL in a Phase 3 Clinical Trial of Darbepoetin alfa (DA) Administered Weekly (QW) or Every 3 Weeks (Q3W) in Anemic Cancer Pts Receiving Chemotherapy.

Until now data on the frequency of adverse events (AEs) at different Hb levels have been lacking; these could help to define the impact of using different therapeutic Hb thresholds for erythropoiesis-stimulating agents. To evaluate the impact of when Hb >12g/dL, we evaluated data from a double-blind, randomized, active-controlled clinical trial of DA in anemic cancer pts (Hb <11g/dL) receiving chemotherapy (Canon, JNCI 2006; 98:373), the most recently conducted trial reflecting approved DA doses (2.25mcg/kg QW and 500mcg Q3W) and current treatment practices in Europe.Methods: This posthoc analysis evaluates transfusion (TFN) and AE data in pts who did or did not achieve Hb >12g/dL during the study. Dose withholding occurred when Hb >13g/dL, and DA was restarted at 60% of previous dose once Hb ≤12g/dL. AEs of interest (hypertension, seizure, ischemic myocardial infarction, and embolism/thrombosis [arterial and venous]) were evaluated.Results: Over 700 pts (50% women) were enrolled. Previously it was reported that the QW and Q3W groups in this study had comparable efficacy (TFN rates from wk 5 to end of treatment, 30% and 23%, respectively), and 23.9% and 21.5%, respectively, reached Hb >13g/dL during the study. In this posthoc analysis, within each dose group and between each group, pts had similar rates of each AE of interest regardless of the maximum Hb achieved on study (Table). 43% in both groups reached Hb >12g/dL; mean (SD) number of QW visits Hb remained above 12g/dL was 5.2 (3.56) and 5.1 (3.89) visits, respectively. Pts with Hb ≤12g/dL had higher rates of death and TFN than those with Hb>12g/dL.Conclusions: Both DA regimens (2.25mcg/kg QW and 500mcg Q3W) were equally effective at preventing the need for TFN. Furthermore, control of Hb in both dose groups was similar as evidenced by the proportion of pts reaching a Hb >12 or 13g/dL. Finally, in this trial, regardless of DA regimen, pts with Hb >12g/dL did not exhibit greater rates of any AE of interest compared to those with Hb ≤12g/dL.TableOutcomes by Maximum Hb on StudyOutcomesMaximum HbDA Dose Group≤ 12g/dL>12g/dLSubjects / Exposure Time [N/E]2.25μg/kg QW202 / 177.5150 / 154.5500μg Q3W200 / 177.7153 / 159.3Deaths [n(r)]2.25μg/kg QW43(0.24)9(0.06)500μg Q3W31(0.17)7(0.04)Transfusions [n(r)]2.25μg/kg QW96(0.54)26(0.17)500μg Q3W85(0.48)15(0.09)Hypertension [n(r)]2.25 μg/kg QW7(3.47)6(4.00)500μg Q3W4(2.00)4(2.61)Seizure [n(r)]2.25μg/kg QW0(0.00)1(0.67)500μg Q3W1(0.50)0(0.00)Ischemic myocardial infarction [n (r)]2.25μg/kg QW2(0.99)1(0.67)500μg Q3W4(2.00)1(0.65)Embolism/thrombosis (Arterial and Venous) [n (r)]2.25μg/kg QW17(8.42)11(7.33)500μg Q3W16(8.00)14(9.15)N = Number of pts evaluable; E = Total 16 person week exposure period; n = Number of pts experiencing event; r = Exposure adjusted pt incidence rate based on the number of pts with AEs in a 16-week time period (r=n/E).

Evaluating the Safety of Erythropoiesis-Stimulating Agents (ESAs) in Patients with Breast Cancer, Lung Cancer, and Hematologic Malignancies: A Meta-Analysis of Randomized, Controlled Trials.

Background: Recent clinical trial data have generated safety concerns regarding ESA use, particularly as to whether the results observed in certain patients with breast cancer, lung cancer, and hematologic malignancies are generalizable to all patients with those tumor types. It is critical that the results of these studies are appropriately integrated into the total body of evidence in order to enable balanced conclusions to be drawn. We conducted a systematic literature review to assess the safety and efficacy of ESA therapy in patients with breast cancer, lung cancer, and hematologic malignancies.Methods: The search was aligned with that conducted by the Cochrane Collaborative group (Bohlius 2006) and was therefore limited to randomized, controlled clinical trials in cancer patients that compared the use of ESAs with either observation (RBC transfusion as required) or placebo and that collected survival data (either long-term or during the study period). Results from trials were meta-analyzed using Comprehensive Meta-Analysis v 2.2 software. Heterogeneity between studies was evaluated using a chi-square test (Q). Random and fixed-effects models were used to estimate an overall odds ratio and 95% confidence interval; the inconsistency statistic, I2, is also provided.Results: For breast cancer, seven studies were identified. Meta-analysis of data from these studies indicated an overall neutral risk of death for patients receiving ESAs, despite the large contribution (weighted at about 40% of the overall result) of the BEST study results (Leyland-Jones, 2005) (Table). Five ESA-controlled lung cancer studies were identified in CIA, one in radiotherapy, and one in anemia of cancer (AOC). In each of the studies in CIA, the ESA groups had neutral survival risks relative to the control group. Meta-analysis of the CIA, radiotherapy, and AOC lung cancer data combined indicated an overall neutral risk of death for patients receiving ESAs (Table). For hematologic malignancies, eight studies were identified (one of which had no deaths). Meta-analysis indicated an overall neutral risk of death for patients receiving ESAs (Table).Conclusions: The results of some studies have suggested a detrimental effect on survival associated with ESA use in certain patients with breast, lung, and hematological malignancies. However, results do not appear to be generalizable to similarly designed, randomized controlled trials conducted in the same tumor types. Additionally, when these studies are integrated into the total body of evidence, ESAs have a neutral effect on survival in these patients. [Display omitted]

About the infrequent thrombotic events during erythropoietin therapy of anemic ovarian cancer patients with chemotherapy

Thrombotic events are infrequently observed in erythropoietin treatments for the anemia in tumorous patients with chemotherapy. The manufacturers call attention to this possible side effect of all kind of such drugs. To estimate the amount of thrombotic events in erythropoietin administrations during epoetin treatments for ovarian cancer patients treated with antineoplastic drugs. 275 ovarian cancer patients were treated with erythropoietin in the Gynecologic Department at the National Institute of Oncology, Budapest, in the period between 2000 and 2006: 52 of them were given epoetin-alfa, 157 of them epoetin-beta and 66 of the patients received darbepoetin-alfa. Median age of the patients was 60 (ranges 22 and 84) years. Thrombotic events were detected in 3 patients out of the 275: one with epoetin-alfa and two times with epoetin-beta treatment (3/275 = 1,1%). No definite causal relationship was confirmed between the thrombotic events and the erythropoietin drugs. Thrombosis was infrequently monitored among the authors' patients similarly to the literature data.

Cost-effectiveness of darbepoetin alfa (DA) 500 mcg every three weeks (Q3W) with IV iron compared to DA Q3W alone in cancer patients (pts) with chemotherapy-induced anaemia (CIA)

19531 Background: IV iron supplementation during erythropoiesis-stimulating agent treatment in anaemic cancer pts may help to optimize anaemia management. We assessed the cost-effectiveness of DA Q3W with IV iron (net 200 mg Q3W; DA+IV iron) to DA Q3W without IV iron (standard practice [SP]= oral iron allowed; DA+SP) from a French societal perspective. Methods: A prospective 16-week, randomized, open-label, multicenter study in 396 pts with non-myeloid malignancy and CIA (hemoglobin [Hb] &lt; 11g/dL) was conducted to evaluate the safety and efficacy of DA+IV iron vs. DA+SP. Data collected include: cumulative doses (IV iron, oral iron, and DA), number of transfusions, and Hb values. Quality adjusted life years (QALY) weights were obtained using the EQ-5D at baseline and at end of treatment. The medical resources used for one DA administration and one transfusion, including pts’ time, were determined by a panel of 20 French clinical experts. Costs were applied to both time (valued at the gross hourly wage) and medical resources (extracted from official sources: AMELI; INSEE). Effectiveness was expressed in average Hb values over the treatment period and the change from baseline in QALY weights. A 5,000- replication probabilistic sensitivity analysis was performed with RISK® after applying distributions to medical resources used and effectiveness parameters. Results: Compared to DA+SP, DA+IV iron showed higher average Hb values (+0.2 g/dL [95% CI: -0.0, 0.4]; 10.9g/dL [10.8, 11.1] vs. 11.1g/dL [11.0, 11.3] respectively), higher QALY weights (+0.017 [-0.028, 0.064]; 0.016 [-0.019, 0.050] vs. 0.033 [0.002, 0.064]) and lower cost (-647.5€ [-938.0, -352.4]; 4,788.3€ [4,561.2, 5,018.2] vs. 4,140.8€ [3,955.4, 4,319.8]). Probabilistic sensitivity analysis revealed that DA+IV iron had a 94% chance of a higher average Hb value and lower costs and 73% chance of a higher QALY level and lower costs. Conclusions: DA Q3W with IV iron is a cost effective alternative to Q3W without IV iron. Further studies in this patient population are needed to determine whether systematic administration of IV iron with DA Q3W will demonstrate cost savings, higher average Hb values, and more QALYs. No significant financial relationships to disclose.

Efficacy and Safety of Every-2-Week Darbepoetin Alfa in Patients with Anemia of Cancer: A Controlled, Randomized, Open-Label Phase II Trial

This randomized, controlled trial evaluated the effect of darbepoetin alfa on hospitalization days, transfusion requirements, hemoglobin levels, and fatigue in patients with anemia of cancer (AOC). Eligible patients were anemic (hemoglobin <or=11 g/dl) due to cancer, >or=18 years old, and had not received chemotherapy or radiotherapy within 4 weeks of study screening. Patients were randomized 4:1 to receive darbepoetin alfa, 3.0 microg/kg every 2 weeks (Q2W) (n = 226), or observation only for 12 weeks (n = 59), followed by an optional 9 weeks of darbepoetin alfa, 3.0 microg/kg Q2W. Endpoints were compared between the two treatment arms at week 13. A planned interim analysis indicated that assumptions regarding hospitalization in the study design were incorrect, so the study was terminated early. Therefore, results for the primary endpoint should be interpreted cautiously. The hospitalization rate was similar (0.5 days) for both the darbepoetin alfa and observation groups (p = .73). Transfusion incidence (weeks 5-12) was significantly lower for darbepoetin alfa patients (8%) than for observation patients (22%) (p = .0092). By week 13, hemoglobin increased by 2.1 g/dl in patients receiving darbepoetin alfa, compared with 0.1 g/dl in the observation group p < .0001. Hemoglobin improvements were paralleled by an increase in Functional Assessment of Cancer Therapy-Fatigue score (mean change in score at week 13: darbepoetin alfa, 6.0; observation, 2.2; p < .05). Darbepoetin alfa Q2W can significantly improve hemoglobin levels and reduce transfusion requirements in patients with AOC, resulting in significant improvements in health-related quality of life.

Treating Anemia of Cancer with Darbepoetin Alfa Administered Every 4 Weeks: Final Results from a Phase 2, Randomized, Double-Blind, Placebo-Controlled Study in Cancer Patients Not Receiving Chemotherapy and/or Radiotherapy.

Darbepoetin alfa (DA) is an erythropoiesis-stimulating agent (ESA) approved in the USA for treating chemotherapy-induced anemia. However, cancer patients (pts) not receiving chemotherapy can still develop anemia of cancer (AoC), which is often not treated (Ludwig et al. Eur J Cancer. 2004; 40:2293–2306). As pts with AoC are not receiving chemotherapy or radiotherapy and may have few clinic visits, using an ESA with a long dosing interval, such as once monthly (Q4W), may be optimal for these pts. Results from a prior study suggested that Q4W dosing of DA is feasible since 61% of pts (n=21) with AoC receiving 6.75mcg/kg DA Q4W achieved a hematopoietic response (≥2g/dL hemoglobin [Hb] rise from baseline or Hb ≥12g/dL without a red blood cell transfusion in the prior 28 days) (Smith et al. Br J Cancer. 2003; 88:1851–1858). Here we report the final results of a phase 2, randomized, double-blind, placebo-controlled study of DA Q4W in pts with AoC. Pt eligibility included ≥18 years, non-myeloid malignancy, AoC (Hb ≤11g/dL), and no chemotherapy and/or radiotherapy within 30 days of screening or during the study. Pts (n=220) were randomized 3:1 to DA (6.75mcg/kg) or placebo (PBO), with stratification based on screening Hb (<10g/dL or ≥10g/dL). Pts received blinded treatment (DA or PBO) subcutaneously Q4W for 13 weeks (4 total doses); end of study was week 17. The primary endpoint was the percentage of pts with a hematopoietic response. Of the 162 DA pts, 63% were female, 73% were white, and the mean (SD) age was 70 (12) years; the 56 PBO pts had similar demographics. The Kaplan-Meier percentage (KM%) of pts with a hematopoietic response (Table) differed significantly between the DA and PBO groups (% difference [95% CL]=44% [30, 58]; p<0.001). The two groups also differed significantly in the KM% of pts who achieved the target Hb of 11g/dL (% difference [95% CL]=38% [22, 54]; p<0.001). Adverse events (AEs) occurred in 71% DA pts (116/164) and 72% PBO pts (39/54); the most common AE was fatigue. The incidence was 3% vs 2% for treatment-related AEs and 28% vs 28% for serious AEs in the DA and PBO groups, respectively. In 30% DA pts and 4% PBO pts, Hb reached >13g/dL. Serious thromboembolic events (deep vein thrombosis, cerebrovascular accident, and pulmonary embolism) occurred in 2.4% DA pts and in 0% PBO pts. In summary, DA Q4W appeared to be effective and well tolerated in this study for the treatment of AoC.Summary of Hb ResultsDAPBOn=162n=56Hematopoietic ResponsePts eligible for hematopoietic response analysis, n15854KM% (95% CL) pts with hematopoietic response69% (61, 77)24% (12, 36)Target HbPts eligible for target Hb analysis, n13949KM% (95% CL) pts achieved target Hb (11g/dL)85% (79, 92)50% (34, 66)Mean (SD) Hb after target achieved, g/dL11.9 (0.8) [n=133]11.3 (0.8) [n=28]Change in Hb from Baseline to Week 17 (LVCF*)Pts eligible for analysis of change in Hb, n15854Mean (SD) baseline Hb, g/dL10.1 (0.8)10.2 (0.8)Mean (SD) Hb change (baseline to week 17), g/dL1.3 (1.4)0.2 (1.0)*LVCF=Last value carried forward

Weekly (QW) epoetin alfa (EPO) in prostate cancer (PC) patients (pts) with anemia not receiving chemotherapy (CT) or radiation therapy (RT)

14634 Background: While EPO is widely used in the management of CT-related anemia, anemia in cancer pts may stem from causes other than CT. Tumor invasion of the bone marrow and cytokine-mediated inhibition of erythropoiesis are among the many disease-related causes of anemia in cancer. Data evaluating the use of EPO in pts not receiving CT or RT, particularly in specific tumor types, would be important information to healthcare providers. Methods: An open-label, prospective, non-randomized, multicenter pilot study was conducted to evaluate the efficacy and safety of EPO 40,000 U QW in anemic (hemoglobin [Hb] ≤ 11 g/dL) cancer pts not receiving CT or RT1. (Blood 2004;104:abstract 4223.) Treatment duration was up to 12 wks with a 4-wk post-treatment observation period. Primary efficacy endpoint was hematopoietic response during the treatment period (% of pts achieving a ≥ 1 or ≥ 2 g/dL Hb increase from baseline [BL]). Secondary endpoints included change from BL in quality of life as measured by the Linear Analog Scale Assessment (LASA). This is a retrospective subset analysis of PC pts (n = 24) enrolled in the prospective study. Results: For the safety population (all pts who received ≥ 1 EPO dose, n = 23), mean age was 71.4 ± 6.8 yrs; 21 (91.3%) had ECOG status of 0 or 1; and mean BL Hb was 10.4 ± 0.8 g/dL. Of 21 pts evaluated for efficacy, 17 (81.0%) achieved Hb increase from BL ≥ 2 g/dL, while 19 (90.5%) achieved ≥ 1 g/dL by wk 17/early withdrawal. EPO dose was increased in 5 (23.8%) pts (to 60,000 U for Hb increase &lt; 1 g/dL after 4 wks) and held in 16 (76.2%) pts (due to Hb &gt; 13 g/dL, with dosing resumed when Hb was ≤12 g/dL, at 30,000 U from 40,000 U or at 40,000 U from 60,000 U). Both Wk 9 and 17 LASA scores increased significantly from BL in all categories (Energy Level, Daily Activities, and Quality of Life; P &lt; 0.001). 15 of 23 pts (65.2%) had at least one adverse event (AE); 4 (17.4%) pts had at least one serious AE. No clinically relevant thrombotic vascular events were noted. No pt received transfusion. 5 pts discontinued: 2 for AEs, 1 at pt request, and 2 at study sponsor request. Conclusions: This retrospective analysis suggests that EPO 40,000 U QW is safe and effective for treating anemia in PC pts not receiving CT or RT. [Table: see text]

Prevalence, severity, and evolution of anemia in colorectal cancer patients receiving radiation therapy with/without chemotherapy: a retrospective analysis

13510 Background: Colorectal cancer (CRC) patients frequently present with anemia. Anemia may also develop or be exacerbated in CRC patients as a consequence of treatment with radiation therapy (RT) with or without (±) chemotherapy (CT). A better understanding of the relationship between anemia and RT ± CT is important as several studies have found that hemoglobin (Hb) levels are predictive of RT outcomes and that low Hb levels can diminish patient quality of life (QOL). However, the prevalence and evolution of anemia before and during RT ± CT are poorly characterized in CRC patients. Methods: Prospectively collected data from 81 CRC patients who received 10 weeks of curative-intent RT alone (26%) or in combination with CT (74%) were analyzed retrospectively to determine prevalence, severity, patterns and contributing factors of anemia. Results: Prior to RT ± CT, 38% of patients (n = 71, evaluable population) were anemic (defined as Hb ≤12 g/dL) and by the end of treatment, 61% were anemic (including 41% of patients not anemic and 93% anemic pre-treatment). A significant (P &lt;.001) decrease in mean Hb for all patients was already apparent after &lt;5 weeks RT ± CT, ie, from 12.6±2.0 g/dL to 11.5±1.8 g/dL, and the decrease in Hb remained consistent over time (see Table). The greatest Hb decrease was noted in patients not anemic pre-treatment, although not all became anemic. Multivariate analysis using logistic regression identified pre-treatment anemia (P = .0006) and age (P = .02) as the factors most strongly associated with intra-treatment anemia. Conclusions: Because anemia can adversely affect QOL and possibly also treatment outcomes in cancer patients, this condition needs to be addressed as part of the overall management of anemic colorectal cancer patients. [Table: see text] [Table: see text]

Preoperative erythropoiesis stimulation in anaemic colorectal cancer patients. Which patients do not respond?

Preoperative erythropoiesis stimulation in anaemic colorectal cancer patients. Which patients do not respond?

A controlled, randomized, open-label study to evaluate the effect of every-2-week darbepoetin alfa for anemia of cancer

8084 Background: Patients (pts) with cancer who are not receiving chemotherapy (ctx) or radiotherapy (rtx) often develop anemia. A previous randomized, controlled trial evaluating the effect of recombinant human erythropoietin therapy vs placebo on transfusion (tfn) incidence in this pt population failed to show a significant reduction in tfn requirements in treated pts, relative to control (Abels, 1991). This multicenter, randomized, controlled, 25-week (wk) study is closed to enrollment (n = 298) and was designed to assess the effect of darbepoetin alfa (DA; Aranesp®) in pts with anemia of cancer (AOC) with respect to hospitalization, incidence of tfn, and pt-reported outcomes. Methods: Eligible pts (anemia [hemoglobin (Hb) ≤ 11 g/dL]) due to cancer or prior ctx and/or rtx; had no ctx or rtx within 4 wks before screening or during the study) were randomized 4:1 to DA 3.0 mcg/kg every 2 weeks [Q2W] for 21 wks (DA arm) or 12 wks of observation followed by 9 wks of DA 3.0 mcg/kg Q2W (control arm). Data were analyzed using an intent-to-treat approach. Results are provided for all pts and stratified by baseline (BL) Hb category. Results: Data through the comparative phase (first 12 wks) were analyzed for the first 170 pts (135 DA, 35 control) enrolled. BL Hb was 10.2 (SD: 0.9) in the DA arm and 10.3 (0.9) in the control arm. Efficacy results (with 95% CL) are shown below. The safety profile was as expected for this population. Conclusions: These results show that AOC pts treated with darbepoetin alfa Q2W (vs no treatment) had marked improvements in Hb corresponding to clinically meaningful improvements in fatigue and a substantial reduction in tfn requirements. Importantly, the stratified analysis suggests that pts with AOC experience important clinical benefits, regardless of BL Hb category; however, earlier intervention (Hb >10 to <11g/dL) may optimize anemia management for this pt population. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen Amgen Amgen

A controlled, randomized, open-label study to evaluate the effect of every-2-week darbepoetin alfa for anemia of cancer

8084 Background: Patients (pts) with cancer who are not receiving chemotherapy (ctx) or radiotherapy (rtx) often develop anemia. A previous randomized, controlled trial evaluating the effect of recombinant human erythropoietin therapy vs placebo on transfusion (tfn) incidence in this pt population failed to show a significant reduction in tfn requirements in treated pts, relative to control (Abels, 1991). This multicenter, randomized, controlled, 25-week (wk) study is closed to enrollment (n = 298) and was designed to assess the effect of darbepoetin alfa (DA; Aranesp®) in pts with anemia of cancer (AOC) with respect to hospitalization, incidence of tfn, and pt-reported outcomes. Methods: Eligible pts (anemia [hemoglobin (Hb) ≤ 11 g/dL]) due to cancer or prior ctx and/or rtx; had no ctx or rtx within 4 wks before screening or during the study) were randomized 4:1 to DA 3.0 mcg/kg every 2 weeks [Q2W] for 21 wks (DA arm) or 12 wks of observation followed by 9 wks of DA 3.0 mcg/kg Q2W (control arm). Data were analyzed using an intent-to-treat approach. Results are provided for all pts and stratified by baseline (BL) Hb category. Results: Data through the comparative phase (first 12 wks) were analyzed for the first 170 pts (135 DA, 35 control) enrolled. BL Hb was 10.2 (SD: 0.9) in the DA arm and 10.3 (0.9) in the control arm. Efficacy results (with 95% CL) are shown below. The safety profile was as expected for this population. Conclusions: These results show that AOC pts treated with darbepoetin alfa Q2W (vs no treatment) had marked improvements in Hb corresponding to clinically meaningful improvements in fatigue and a substantial reduction in tfn requirements. Importantly, the stratified analysis suggests that pts with AOC experience important clinical benefits, regardless of BL Hb category; however, earlier intervention (Hb >10 to <11g/dL) may optimize anemia management for this pt population. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen Amgen Amgen