Intravenous Iron Monotherapy for Absolute and Functional Iron Deficiency Anemia in Cancer Patients

Iron deficiency anemia (IDA) is common in cancer patients. The Hemoglobin (Hb) response rate in cancer patients with IDA who receive an erythropoiesis stimulating agent (ESA) ranges from 25 – 65% and is increased to 68 – 93% when intravenous (IV) iron is added to the ESA. Interestingly, there have been no studies to date that have evaluated Hb response to IV iron monotherapy for the treatment of IDA in cancer patients. The National Comprehensive Cancer Network (NCCN) recommends treating absolute IDA (AIDA, serum ferritin < 30 ng/mL and TSAT < 15%) with iron monotherapy, preferably IV. However, the NCCN recommends that functional IDA (FIDA, serum ferritin ≤ 800 ng/mL and TSAT < 20%) be treated with both IV iron plus an ESA. Unfortunately, ESAs carry black box warnings for increased mortality, cancer progression, and venous thromboembolism. Therefore, it is important to explore other ways to more safely treat IDA in cancer patients. The objective of this study was to evaluate the Hb response rate to IV iron monotherapy in cancer patients with AIDA and FIDA.

A retrospective chart review was performed at the Huntsman Cancer Institute between January 2006 and June 2011 in cancer patients with AIDA or FIDA who were treated with low molecular weight iron dextran (LMWID) monotherapy. Patients were excluded if they had a ferritin > 800 ng/mL or TSAT ≥ 20%, received an ESA within 6 weeks prior to or within 4 weeks after the LMWID infusion, or received a packed red blood cell transfusion prior to the LMWID infusion without a documented post- transfusion, pre-LMWID infusion Hb. The primary outcome was the proportion of patients with a Hb response defined as an increase of at least 1 g/dL within 6 weeks post IV iron infusion. The secondary outcome was the Hb response within 6 weeks stratified by dose of IV iron.

Two hundred patients received LMWID at our institution within the specified time period. However, 182 patients were excluded because they did not have active cancer, did not have a definitive diagnosis of AIDA or FIDA, or received concomitant therapy with an ESA. Eighteen patients with either a hematologic or solid malignancy were included. Thirteen patients had AIDA and 5 patients had FIDA. Eight of the 13 (62%) patients in the AIDA group had a Hb response. The median Hb increase in the AIDA group was 1. 3 g/dL (p < 0. 0001). A Hb response was observed in 4 of the 5 (80%) patients in the FIDA group. The median Hb increase in the FIDA group was 1. 8 g/dL (p = 0. 0224). Of the 8 patients with AIDA achieving a response, 4 received less than and 4 received more than the calculated total IV iron dose (equation per package insert). Of the 4 patients achieving a Hb response in the FIDA group, 3 received less than and 1 received equal to the calculated total dose. The overall Hb response rate to IV iron monotherapy for both groups was roughly 67% which is greater than the Hb response rate reported with ESAs alone. See Table 1 for individual patient details.

Although our study has limited patient numbers, this is the first data suggesting that IV iron without an ESA may be an effective treatment for both AIDA and FIDA in anemic patients with a variety of malignancies. IV iron monotherapy may eliminate the need for an ESA. This hypothesis should be tested in larger studies.

Off Label Use: The total dose infusion of low molecular weight iron dextran is not an FDA approved dosing regimen. However, it is commonly used in practice and has been used in other studies. Rodgers:American Regent: Consultancy.