Session: 201. Granulocytes, Monocytes, and Macrophages: Poster I
Hematology Disease Topics & Pathways:
Biological, Adult, Diseases, Therapies, Genetic Disorders, Adverse Events, Pediatric, Young Adult, immunotherapy, Study Population, Clinically relevant
METHODS The French Severe Chronic Neutropenia Registry (FSCNR) since 1993 prospectively monitors patients with ChrN and collects routinely information about G-CSF therapy (type of product including the Brand names, dose per injection, number of injections, duration of the period of daily treatment, infections, blood counts, side effects..)(1). On 1 October 2019, the FSCNR had enrolled 1068 patients with ChrN (idiopathic neutropenia(2) n=231 and Congenital neutropenia(3) n=837 patients). To take into account individual changes in G-CSF regimens, for a given patient, treatment was divided into elementary periods during which the characteristics of G-CSF treatment remained constant. Several parameters were calculated by summing up the elementary periods: duration of follow-up after G-CSF start, Cumulative duration, Cumulative dose, Time averaged dose (TAD). Three treatment groups were defined according to the type of G-CSF received: “group F” for patients who received only F, “group L” for patients who received only L , “group FL” for patients who received both F and L in succession. As there are no guidelines for GCSF prescription (F or L), even if L is here prescribed off-labelled, treating physician made is own choice. Because PegF have a very specific PK profile, we excluded the Peg F periods from this analysis (only 29 patients have received PegF as part of their therapy). The analysis presented here is limited only to the “L group’, the “F group’ and the “FL group’. 434 of the 1068 patients with ChrN have received a GCSF therapy: 172 received Lenograstim alone (group L), 148 Filgrastim alone (group F) and 112 received both cytokines consecutively (group FL).
RESULTS: The key parameters defining the disease, the severity of the clinical and hematological presentation, the median neutrophil count, the proportion of patients with bone marrow blockage and the number of severe and oral infections was similar between the 3 patient groups (table 1). For group FL and more over the L group the median age at the start of G-CSF was younger (p<0.001). Such differences may be related to the availability, for L, of a smaller vial, more adapted to the prescription of GCSF in infants. At contrary, the TAD received by the patients was similar between the 3 treatment groups (5.5 µg/kg vs 5 and 5 in FL, L and F respectively, p=0.14). With regards to the efficacy, by taking in consideration both hematological parameters like neutrophil count, the rate of failure, as well clinical endpoints like the rate of stomatological and severe infections, we failed to find any differences between L and F groups and among the FL group, between F and L periods. Lastly, rate of side effects, both major side effects like death (mostly not related to GCSF), Myelodysplasia or leukemia, or mild, like bone pains were not different between F and L. Patients from FL have a higher rate of side effects, probably because physicians tried to avoid minor side effects by drug switch.
Conclusions: The efficacy profile as well as the safety profile of Lenograstim is indistinguishable from that of Filgrastim in ChrN. The availability of Lenograstim in small vial represent a pragmatic advantage to treat infants as well as patients who are requiring only little amount of GCSF.
References
- J. Donadieu et al., Haematologica 90, 45 (2005).
- F. Sicre De Fontbrune et al., Blood 126, 1643 (2015).
- J. Donadieu, B. Beaupain, O. Fenneteau, C. Bellanne-Chantelot, Br. J. Haematol. 179, 557 (2017).
Acknowledgments: The French SCN registry is supported by grants from Amgen, Chugai, Prolong Pharma, X4 Pharma, Inserm, the Association 111 les Arts, the Association RMHE, the Association Sportive de Saint Quentin Fallavier. The authors thank the association IRIS and Mrs Grosjean and Mr Gonnot(ASSQF), the association Barth France for their support.
Disclosures: Sicre de Fontbrune: Alexion Pharmaceuticals Inc.: Honoraria, Research Funding.
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