Incidence of Febrile Episode During Stem Cell Mobilization (SCM) After High Dose Ciclophosphamide Chemotherapy (HD-CTX) and G-CSF (filgrastim or lenograstim) Administration in Multiple Myeloma (MM) Patients: II Interim Evaluation

Introduction: Clinical use of G-CSF in pts with high grade chemotherapy induced neutropenia does not conduce to a reduction of the incidence of febrile episodes (FE). This paradox may be explained by the acquisition of a defective chemotaxis by neutrophils (PMN) exposed to filgrastim (Fil), due to a higher adhesivity and cytoscheletric alterations. Lenograstim (Leno), a glicosilated form of G-CSF, is able to stimulate PMN production, manteining in vitro all the functional capabilities. On these bases, we hypotized that Leno may prevent FE and reduce their lasting in pts with chemotherapy derived neutropenia.

Patients and methods: starting from April 2005, 105 MM pts achieving HD-CTX for SCM were enrolled in 12 Centers. Treatment plan consisted in: HD-CTX (3 or 4 g/sqm) on day 1, G-CSF (random: Fil or Leno) 30 MU/day from day +4 to +9, 60 MU/day from day +10 to the achievement of an optimal CD34+ cell count for staminoapheresis. Random, 1:1, was effectuated on the base of a generated random list. FE, significant if equal or higher than 38 °C for at least 2 different determinations, were recorded till day +30. Primary endpoint is the incidence of FE; secondary endpoints are the duration of FE, efficacy in the CD34+ cell mobilization, time to mobilization.

Results: 105 pts were enrolled. All pts underwent post-chemo grade 4 neutropenia and G-CSF was administred starting from day +4. FE were recorded in 23 pts, 14 in the Fil arm (53 total pts) and 9 in the Leno arm (52 total pts). The global fever incidence was 21.9%, 26.4% with Fil and 17.3% with Leno, with a 9.1% difference. Average days with fever are 4.00 with Fil and 3.67 with Leno. Related to the neutropenia grade, 8 FE are recorded with Fil and 1 FE with Leno with absolute PMN count >500/μL (grade 4); 7 episodes with Fil vs 1 with Leno when PMN are >1000/μL (grade 3–4). CD34+ SCM occurs in after an average time of 10.3 day with Fil and 9.8 day with Leno, with an higher absolute count with Leno when compared to Fil: 131.9 CD34+/μL (range 40–640) vs 111.6 (range 40–616) CD34+/μL.

Conclusions: Leno is associated with a reduced incidence (17.3% vs 26.3%) of FE in MM patients undergoing to HD-CTX and SCM when compared to Fil. FE are recorded with Fil even in presence of PMN confirming the functional block by Fil on PMN documented in vitro. CD34+ mobilization occurs shorter and with higher efficiency with Leno when compared to Fil. On these evidences, patients’ enrollment will continue to 180 to validate these results.