Fixed-Dose Single Agent Pegfilgrastim for Peripheral Blood Progenitor Cell Mobilization in Patients with Multiple Myeloma (MM).

High-dose chemotherapy and autologous peripheral blood progenitor cell (APBPC) transplantation is an effective treatment for MM. Progenitor cells are generally mobilized in to the blood by administration of filgrastim alone or after chemotherapy. Since the half-life of filgrastim is 3–4 hours, daily SC injections are required until completion of apheresis. Pegylated filgrastim (Neulasta™; Amgen Inc., Thousand Oaks, CA, USA) is a covalent conjugate of filgrastim and monomethoxypolyethylene glycol, with a half-life of about 33 hours. Preliminary data suggests that a single SC injection of pegfilgrastim may mobilize progenitor cells without added toxicity and thus avoid the need for repeated injections. We performed a phase II study of pegfilgrastim administered as a single SC injection to mobilize APBPC.

PATIENTS AND METHODS. Patients with MM, who were to undergo high-dose chemotherapy and APBPCT were studied. Patients were required to have a PS of < 3 (ECOG), adequate hematological (WBC > 3.5 x 10⁹/l; platelet count > 100 x 10⁹/l) and adequate organ function. Patients whose prior therapy included thalidomide, dexamethasone and bortezomib were eligible. The protocol was IRB approved and all patients signed informed consent. Because of the rare cases of splenic rupture associated with high-dose filgrastim, patients were also required to have a maximum spleen size of < 12 cm in the greatest dimension by radiographic imaging as stipulated by the FDA. All patients were given single SC fixed-dose of 12 mg pegfilgrastim. Circulating CD34+ cell levels were assessed daily starting day +2 after the pegfilgrastim. Leukapheresis was started when the PB CD34+ count was greater than 15/μL. Leukapheresis employed standard procedures using 3 times the total blood volume. Daily leukapheresis was performed until the target pheresis cell dose of at least 6 x 10⁶ CD34+ cells/kg was reached for patients planned for tandem APBPCT and at least 3 x 10⁶ for single transplant procedure. High-dose chemotherapy comprised of melphalan (200 mg/m²) alone or in combination with arsenic trioxide. All patients received filgrastim 5 mcg/kg/day SC starting at day 0 after stem cell infusion.

RESULTS: Between 1/04 and 3/05, 19 patients (13 M /6 F) with a median age of 57.5 years (range, 34.5–77.4) were entered on the study. The median time to reach a PB CD34 count of 15/μL was 3 days (range, 2–4). The median number of leukapheresis procedures required was 2 (range, 1–5). The median collection of CD34+ cells was 8.4 x 10⁶ (range, 4.1–15.8). The median CD34+ cell dose collected/L of blood processed was 19.3 (range, 6.4 – 77.4). Most common toxicity was bone pain in 6/19 patients (maximum grade 3). Reversible liver enzyme elevations were seen in all patients. At the time of this report 15/19 patients have undergone autologous transplantation with a follow-up of 100 days. The median CD34+ cell dose infused was 4.2 x 10⁶/kg (range, 2.6–9.4). Median time to ANC ≥ 0.5 x 10⁹/l was 10 days (range, 9–11 days) and median time to platelet counts ≥ 20 x 10⁹/l was 11 days (range, 0–17).

CONCLUSIONS: A single fixed-dose of pegfilgrastim was effective in mobilizing adequate peripheral blood progenitor cells in patients with MM. The efficacy and toxicity profile was similar to that seen with filgrastim. Rapid and sustained engraftment was seen in all patients following autologous transplantation.