Long-Term Safety and Efficacy of Single Administration of a Fixed Dose Pegfilgrastim (Neulasta) in Inducing Neutrophil Count Recovery after ABVD Chemotherapy in Patients with Hodgkin Lymphoma.

Abstract

Pegfilgrastim (Neulasta) is a pegylated form of G-CSF that has a long half-life allowing for a single administration per chemotherapy cycle. Although the safety and efficacy of pegfilgrastim has been established in association with chemotherapeutic regimens that are repeated every 3 weeks, its safety in patients receiving chemotherapy regimens every 2 weeks is currently under investigation. Of concern is the possibility of stem cell damage because of the long half life that may overlap with subsequent courses of chemotherapy. ABVD chemotherapy is widely used for the treatment of patients with Hodgkin disease. Up to 65% of patients receiving ABVD will require growth factor support to 1) maintain dose intensity 2) to prevent neutropenic fever and 3) to prevent delays in chemotherapy administration. In this study, we used a single dose per cycle of 6 mg pegfilgrastim in first and subsequent cycles of ABVD. Patients were eligible if they were older than 16 years and had previously untreated Hodgkin's disease patients who are scheduled to receive standard ABVD chemotherapy, adequate bone marrow reserve (ANC > 1,000/uL, Platelet > 100,000/uL, left ventricular ejection fraction > 50%, serum creatinine < 2 mg/dl, serum bilirubin < 2 mg/dl. They were excluded if they had HIV infection, were pregnant women and women or child bearing age who are not practicing adequate contraception, had prior chemotherapy, severe pulmonary disease including COPD and asthma, or history of prior sensitivity to E.coli derived products. All patients received one fixed dose of 6 mg pegfilgrastim 24 hours after ABVD therapy. CBC was performed on a weekly basis, until completion of therapy, and then was monitored every 3–4 months thereafter. Twenty-five patients are enrolled, all of whom are evaluable for efficacy and toxicity. Median age is 26 (range; 19 – 81 years). Men = 14, women = 11. Twenty three pts completed at least 3 full cycles (6 doses of ABVD), and thirteen Pts completed 6 cycles. A total of 225 doses of ABVD are administered. Day 14 ANC count below 1,000/uL occurred in only 5 doses of ABVD (2%). Non-neutropenic infection developed with 7 doses (3%) requiring delay in the subsequent dose of ABVD beyond day 14. Long-term safety is available on 11 pts who had a follow-up ANC counts beyond one year after completion of ABVD treatment. The median ANC after at least one year of follow up was 2,790/uL (range 1,350 to 7,060/uL). Five pts had a follow up beyond 18 months, and their median ANC was 2,300/uL (range: 1,570 to 3,360/uL). Furthermore, PK data from 5 unselected patients were performed on day 14 following the first cycle of ABVD. In all 5 patients, serum pegfilgrastim levels were below clinically significant levels. Our data demonstrate the efficacy of single dose per cycle of pegfilgrastim in maintaining ABVD dose intensity, keeping therapy on schedule, and preventing neutropenic fever. Furthermore, our preliminary long-term follow up data demonstrate the safety of pegfilgrastim administration in conjunction with standard dose chemotherapy given every 2 weeks.