Epoetin Alfa vs Standard of Care Decreases Number of Packed Red Blood Cell Transfusions in Patients Receiving Hyper-CVAD for Acute Lymphocytic Leukemia, Lymphoblastic Lymphoma, and Burkitt’s Lymphoma.

Background: Anemia is common in patients with acute lymphocytic leukemia (ALL), lymphoblastic lymphoma (LL), and Burkitt’s lymphoma (BL) treated with chemotherapy and is associated with poor cancer control. Studies have shown that even mild correction of anemia has been associated with a significant improvement in quality of life. Although there are studies that show a survival benefit in patients receiving epoetin alfa (EPO), there are at least two randomized trials which reported negative outcomes with respect to progression-free survival in patients with solid tumors treated with EPO. The current standard of care for treatment of anemia in ALL, LL, and BL is packed red blood cell transfusions (PRBC). However, transfusions are time consuming and carry risks of infection and transfusion reaction.

Objectives: To evaluate if EPO 1) decreases number and frequency of transfusions, and 2) adversely influences the complete remission (CR) rate to chemotherapy.

Methods: Patients with newly diagnosed ALL, LL, or BL receiving hyper-CVAD were randomized to EPO vs standard of care within 14 days of starting chemotherapy. EPO dose was 40,000 units SQ weekly and escalated to 60,000 units after four weeks if indicated. Both arms received blood transfusions as per uniform guidelines. Patients were considered evaluable if they had been on the study for at least five weeks.

Results: Forty-six of 70 patients were evaluable and included in this first interim analysis; 23 were treated with EPO. There were 16 ALL, 4 BL, and 3 LL on EPO and 20 ALL, 1 BL, and 2 LL in the standard of care arm. The two groups were comparable in baseline hemoglobin and number of courses of chemotherapy completed. Median age was lower in the EPO arm (32, range 20–71) when compared to the standard of care arm (42, range 16–68; p=0.37). There were more male patients in the EPO arm than standard of care arm (14 vs. 9; p= 0.144). Median baseline erythropoietin level was 299 (range 12–10532) in the EPO arm vs. 104 (range 7–491; p=0.02) in the standard of care arm. The median total number of PRBC units in the EPO group was 12 (range 4–23) compared with 16 (range 9–31) in the standard of care group (p= 0.01). The median number of transfusion events (frequency) was 7 (range 2–13) in the EPO arm compared with 9 (range 4–18) in the standard of care arm (p= 0.03). Time to neutrophil and platelet recovery was comparable in both arms. All patients with ALL had a CR in both arms. On the EPO arm, 1 patient with BL and 1 patient with LL had a partial remission. One patient with LL on the EPO arm had no response to chemotherapy. All patients with BL and LL on the standard of care arm had a CR (p=0.073).

Conclusions:

1. In patients with ALL, LL, and BL on hyper-CVAD, EPO decreased the frequency and number of packed red blood cell transfusions.

2. EPO does not affect recovery of other cell lines.

3. Use of EPO in this patient population does not appear to have an adverse impact on CR rates in patients with ALL. The numbers of BL and LL are too small to draw conclusions regarding effect of EPO on response rates.