Abstract

The safety and efficacy of pegfilgrastim (Neulasta) has been established in association with chemotherapeutic regimens that are repeated every 3 weeks. However, the long-term safety of pegfilgrastim in patients receiving chemotherapy regimens every 2 weeks remains 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 lymphoma (HL). Up to 65% of patients receiving ABVD will require growth factor support to maintain dose intensity, prevent neutropenic fever, and to prevent delays in chemotherapy administration. In this study, we used primary prophylaxis 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 HL 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 approximately 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 after completion of ABVD therapy, 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 ABVD chemotherapy given every 2 weeks.