Lower Leukocytosis with Biosimilar Compared with Originator G-CSF during Autologous Stem Cell Mobilization after Chemotherapy in Lymphoma and Multiple Myeloma Patients. a Pharmacovigilance Study of “Rete Ematologica Lombarda” (FARMA-REL)
Authors: Pelizzari Anna Maria , Tozzi Paola , Bocchio Francesca , Bonfichi Maurizio , Artuso Silvia , Fracchiolla Nicola , Conti Valentino , Ferremi Pierino , Almici Camillo , Bettoni Daria , Orlando Vincenza , Rossi Giuseppe , Muti Giuliana 
Published: October 2019

Abstract
BACKGROUND: Based on therapeutic equivalence extrapolated from originator, the use of biosimilar Granulocyte-Colony Stimulating Factor (G-CSF) in the context of stem cell harvest was approved by the European Medicines Agency (EMA), however “ad hoc” studies are limited.
AIMS: To assess the efficacy and safety profile of biosimilar compared with originator G-CSF on PBSC autologous mobilization in association with chemotherapy (CT) in lymphoma (LY) and multiple myeloma (MM) patients (pts) treated in the Hematology Units of “Rete Ematologica Lombarda” (REL).
PATIENTS AND METHODS: Data retrospectively collected from consecutive pts with Hodgkin disease (HD), non-Hodgkin LY (NHL) and MM undergoing PBSC harvest after CT with biosimilar filgrastim between July 2012 and December 2013 (LY) or June 2014 (MM), were compared with a historical control group treated with originator G-CSF. Biosimilar G-CSF was used at doses ranging from 5 (MM and lymphoma HIV-negative) to 10 mcg/kg/d (lymphoma HIV-positive) subcutaneously, starting from the day after the end of CT until the end of leukapheresis. The Shapiro-Wilk test was used to assess normality of data: p-values were derived from chi-square test for categorical data and from Mann–Whitney U-test for continuous data.
RESULTS: One hundred-five leukapheresis from 96 consecutive pts including 3 HD, 51 NHL (46 HIV-negative and 5 HIV-positive) and 42 MM cases were analyzed. Median age was 53 yrs (19-65) among LY and 63 (43-72) among MM pts. Thirty-two/54 (59 %) and 19/42 (45 %) cases were male, respectively. Mobilization was planned as part of first line CT in 65% of LY pts; only one case was mobilized during 3rd line CT. Forty-five LY cases (47 %) had been previously treated with alkylating drugs (47 %), three (3 %) with fludarabine-containing regimens. All MM pts mobilized after first line CT.
Mobilization started a median of 13 (range 10-21) and 10 (range 10-18) days after CT for LY and MM, respectively; it was completed in a median of one procedure (range: LY 1-4, MM 1-3). Median number of CD34+ cells collected was: 9,1 (range 3,0-47) and 7,8 (range 4,1-12,9) x 106/Kg/pt in LY and MM pts, respectively. Planned end-point was reached in all MM cases and all but 2 LY cases (3 %).
Biosimilar G-CSF use was well tolerated in both LY and MM pts: mild bone pain (WHO grade 1-2) was frequently reported (LY: 16/54, 23 %; MM: 16/42, 38 %); two LY pts needed treatment with acetaminophen for headache (1) and bone pain (1), both WHO grade 3.
Data were compared with a historical control group of 58 LY pts (HD 10, NHL 45, NHL-HIV 3) and 32 MM pts mobilized with originator G-CSF (filgrastim or lenograstim)(Table): while MM cohorts are similar, LY cohorts differed for a higher frequency of mobilization with high-dose cyclophosphamide (2/54, 4 % vs. 14/58, 24 %, p<0.001) and a slight prevalence of HD cases (3/54, 5 % vs. 10/58, 17%, p= 0.053) only. Median number of procedures, CD34+ count peak and CD34+ collected were similar in both groups; however a difference in median WBC count peak during leukapheresis was documented in both cohort, statistically significant in LY, even if treated without cyclophosphamide.
CONCLUSION. We confirm efficacy and safety of biosimilar filgrastim for autologous PBSC mobilization in LY and MM pts. Noteworthy, biosimilar seems to be more selective on CD34+ cells compared with originator G-CSF, inducing efficient CD34+ cells mobilization with lower leukocytosis. This result, confirmed in both LY and MM populations, needs to be proved in larger studies and can play a major role in the setting of voluntary donors.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.