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The Use of Tevagrastim (Biosimilar Filgrastim XMO2) for Hematopoietic Stem Cell Mobilization in HLA Matched Sibling Donors for Allogeneic Stem Cell Transplantation to AML/MDS Patients
G-CSF Filgrastim is widely used for the mobilization of CD34+ HSC. The experience with biosimilar G-CSF agents is limited. We initiated a prospective study assessing Tevagrastim (biosimilar Filgrastim XMO2) for mobilization of CD34+ PB HSC in MRD for alloSCT in 24 pts with AML/MDS (NCT01542944).
Materials and methods
The study was approved by the National Regulatory Authorities and both patients and donors signed an informed consent. The donors, median age 46 years (range, 25–64), F- 14; M- 10 received Tevagrastim (10 μg/kg) BW s.c. BID for 4 days. On the morning of the 5th day they underwent conventional leukapheresis. The target yields of CD34 cell was 5 × 106 CD34+ cells/kg BM of the recipient. The conditioning was myeloablative Bu/Cy (n=10), reduced toxicity Flu/Treo (n=7), Flu/Bu4 (n=3) or RIC Flu/Bu2 (n=4).
Results
Efficacy: 77-1982 × 106 (median 749 × 106) CD34+ were collected. The number of CD34+ cell per kg BW of the pts was 0.93-35.4 × 106 (median 10.2 × 106). Collections contained 144-709 × 108 (median 299 × 108) CD3+ T-cells, 1.74-11.6 ×108 (median 4.4 ×108) per kg BW of the pts and 0.3-11.2x107/kg (median 2.3x107/kg) CD3- CD56+ CD16+ NK cells. The mean number of leukapheresis procedures was 1.3. Engraftment was: ANC >0.5× 109/L and >1× 109/L within a median of 13 days (range, 10–21) and 13.5 days (range, 10–22), respectively. PLT reached counts of >20× 109/L and >50× 109/L within a median of 16 (range, 12–33) and 17 (range, 12–33) days, respectively. The median days of isolation was 10 (range, 6-21). The median number of PC and PLT transfusions was 5 (range, 2-20) and 21 (range, 0-180), respectively. 20/24 (83.3%) pts showed full donor chimerism at 1 month after transplantation, respectively.
Safety: 12/24 donors reported transient arthralgias and 2 developed flu-like syndrome. The main side effects were mucositis (n-15, grade II -9, grade III-IV- 6), infections (n-20) and fluid retention (n-8). One pt suffered from VOD (Grade-I) and 5 pts developed aGVHD (grade II-III) which responded to conventional therapy. In total TRM was 1/24 at d 100. Total 5 pts died from leukemia progression during median 7 (range, 1-16) months; 2 of them died before d 100. 4 pts suffered from chronic, mild GVHD.
Conclusions
Our study with 24 AML/MDS pts, indicates that the G-CSF biosimilar XM02, Tevagrastim is safe and efficient for stem cells mobilization in MRD. The CD34 yield and post transplantation engraftment are similar to those achieved with the human recombinant G-CSF Filgrastim. We have not seen significant differences in the graft CD34+ , CD3+ T and CD16+ NK cell count, the number of leukapheresis procedures and the regeneration of WBC, neutrophils and PLTs in comparison with our historical controls. All patients promptly engrafted, and the donors developed only expected side effects. Neither graft rejection nor side effects occurred more frequently than expected from the standard G-CSF.