Efficacy of Darbepoetin Alfa in the Treatment of Chemotherapy-Induced Anemia in Non-Hodgkin’s Lymphoma.
Authors: Gregory Stephanie A. , Blayney Douglas W. , Vadhan-Raj Saroj , Tomita Dianne K. , Rossi Greg , Mirtsching Barry 
Published: October 2019

Introduction: Chemotherapy-induced anemia is common in patients (pts) undergoing chemotherapy for Non Hodgkin’s Lymphoma (NHL). Darbepoetin alfa (DA) has been shown to increase hemoglobin (Hb), decrease transfusions, and reduce fatigue. NCCN evidence-based guidelines for using erythropoietic agents recommend a target Hb of 11-12g/dL for efficacy and safety. We report here an analysis of the efficacy of DA in achieving and maintaining Hb within the target range in anemic NHL pts undergoing chemotherapy.

Methods: This analysis presents the results of 2 sequentially conducted, multicenter, open-label studies with pts treated with either DA 3 mcg/kg Q2W (Study 1, SOAR) or DA 200 mcg Q2W (Study 2, SURPASS). Dose withholding rules for Study 1 required DA to be withheld when Hb >14g/dL for women and >15g/dL for men while in Study 2 DA was withheld for any pt with a Hb >13g/dL. This subset analysis involved pts diagnosed with NHL. Eligibility was similar with the 2 studies: ≥18 years, anemic (Hb <11g/dL), with non-myeloid malignancies, and receiving chemotherapy. Hematologic endpoints included Hb at end of study (EOS), percent of pts achieving target Hb (11–12g/dL) and mean Hb after reaching target. Endpoints were analyzed by the last value carried forward (LVCF) approach where missing Hb values are imputed and without imputation (available data analysis) and analyzed at week 17 unless otherwise noted. Pt reported outcomes were assessed with the FACT-F scale collected at EOS using available data analysis.

Results: This analysis involved 279 pts with NHL (Study 1: n=114; Study 2: n=165). Baseline disease and demographics were similar between the 2 studies. In both studies, DA Q2W was effective in increasing Hb levels into the NCCN recommended target range (Hb >11g/dL) and improving patient reported fatigue. Dose titration rules between the studies seemed to have a different impact in the ability to maintain Hb within the range of 11–12g/dL as recommended by NCCN guidelines. When dose withholding at 13g/dL was used, the average maintenance Hb (ie, the average Hb after achieving target range) was approximately 12g/dL (Study 2) compared with 12.5g/dL if a higher withholding threshold was employed (Study 1). In Study 1, 31% of pts who achieved the target Hb range actually maintained a mean Hb above 13g/dL compared with 11% in Study 2. Interestingly, despite an approximate 1g/dL difference in final Hb achieved, higher average maintenance Hb and higher overall dose, no difference in FACT-F scores for NHL patients was observed between the 2 studies.

Conclusions: Patients with NHL and anemia due to chemotherapy can be effectively treated with less frequent injections by dosing with DA 200 mcg Q2W.

Summary of Endpoints

Study 1 Study 2 N 114 165 Baseline Hb, g/dL (SD) 10.2 (1.1) 10.0 (0.8) Mean Hb (week 17); LVCF imputation, g/dL (SD) 12.4 (2.2) 11.3 (1.7) Mean Hb (week 17); without imputation, g/dL (SD) 13.1 (1.8) 11.9 (1.5) Pts achieving Hb target, % (n) 77% (85) 82% (131) Mean maintenance Hb after achieving target, g/dL (SD) 12.6 (1.1) 11.9 (0.9) Mean change (95% CL) in FACT-F at EOS 6.2 (3.7, 8.7) 6.1 (2.7, 9.4) Mean (SD) Q2W dose, mcg 249.4 (74.6) 184.3 (73.3)