Efficacy and Safety of a Biosimilar Granulocyte-Colony Stimulating Factor for Stem Cell Mobilization before Autologous Hematopoietic Stem Cell Transplantation

INTRODUCTION

Biosimilars are approved biologics with comparable quality, safety and efficacy to a reference product for which patent protection has expired. Biosimilars of recombinant human granulocyte-colony stimulating factor (G-CSF) have been available for more than 8 years now and are widely used in Europe; however, there are still some concerns regarding their long-term safety and immunogenicity.

The objective of this study was to evaluate the efficacy and safety of the biosimilar G-CSF (Zarzio) to mobilize stem cells in the autologous hematopoietic stem cell transplantation (HSCT) setting.

METHODS

We retrospectively reviewed 209 consecutive patients undergoing peripheral blood stem cells harvest between December 2009 and December 2015 using the biosimilar G-CSF.

The target CD34+ stem cell dose at our institution is 2 x 10⁶/kg for autologous HSCT. A survey to evaluate the potential side effects related to the mobilization process was conducted during the follow-up.

RESULTS

The median age at the time of harvest was 56 years old (range: 16-75) and 113 (54,1%) patients were male. The indication for autologous HSCT was lymphoma in 102 (48,8%) cases, plasma cell neoplasm in 90 (43%), acute leukemia in 12 (5,8%), non-haematological malignancy in 3 (1,4%) and autoimmune disorder in 2 (1%). The patients had received one (n=86; 41,1%), two (n=89; 42,6%) or more than two (14,4%) lines of treatment before mobilization. Only 4 (1,9%) cases had not received prior lines of chemotherapy.

Patients were primed with the biosimilar G-CSF alone (n=64) or following a cycle of chemotherapy (n=145). Additional Plerixafor was administered in 31 cases (14,8 %) because peripheral CD34+ count was too low or the patient had poor baseline predictors.

Sufficient CD34+ cells were collected with a single priming procedure in 195 (93,3 %) cases and 14 (6,7 %) underwent a second mobilization. Only 4 (1,9 %) patients did not reached the target CD34+ stem cells dose. The median number of harvest days required per patient was 1 (range: 1-5) and the median total CD34+ cells x 10⁶/kg collected was 4,08 (0,36 - 57,42).

In 18 (8,6%) patients autologous HSCT was cancelled due to disease progression (14 lymphomas, 3 acute leukemias and 1 Waldenstrom macroglobulinemia). The remaining patients (n = 191) received high dose chemotherapy followed by autologous stem cell infusion.

The median CD34+ cells x 10⁶/kg infused was 4,02 (1,79 - 28,71). The median post-HSTC days to neutrophil (>0,5 x 10⁹/l) and platelet (>20 x 10⁹/l) engraftment were 12 (range: 7-31) and 12 (8-60) respectively. Three (1,4 %) patients died before engraftment on days 5, 7 and 8 post-HSCT (2: Toxicity related to the conditioning regimen; 1: Bacterial hemorraghic enterocolitis).

Sixty-four (30,6 %) patients reported bone or muscle pain during the first weeks following the use of the biosimilar G-CSF but no severe adverse effects were reported after a median follow-up of 31 (1 - 75) months.

CONCLUSIONS

The target CD34+ stem cells dose was collected in almost all the cases showing that the biosimilar G-CSF was effective for the mobilization process in our patients.

The biosimilar G-CSF was also safe with only one third of the patients reporting non-severe side effects being the most common bone or muscle pain.