KEY TAKEAWAYS
- The ongoing phase 1/2 study assessed RP-L201-0318 gene therapy using autologous CD34+ cells with a lentiviral vector to recover CD18 expression in pediatric pts with severe LAD-I.
- The study suggested that RP-L201 is safe and effective for treating LAD-I.
Severe leukocyte adhesion deficiency-I (LAD-I) arises from mutations in the ITGB2 gene and is vital for neutrophil function. This severe form, marked by <2% normal CD18 PMN expression, leads to persistent infections, poor wound healing, and high childhood mortality without stem cell transplant. While allogeneic hematopoietic stem cell transplant can cure it, complications arise. RP-L201-0318 gene therapy used autologous CD34+ cells with a lentiviral vector to recover CD18 expression.
The study enrolled patients (pts) older than 3 months with serious LAD-I. Their hematopoietic stem cells (HSCs) were gathered using apheresis after being prepared with granulocyte-colony stimulating factor and plerixafor. These cells were then externally modified with Chim-CD18-WPRE-LV. Before the RP-L201 was administered, a myeloablative busulfan conditioning was done. Afterward, the patients’ health and treatment effectiveness were tracked, looking at factors like survival past two years of age, one year after the treatment, changes in blood PMN CD18 levels, vector copy numbers in the blood, better neutrophil counts, fewer infections or hospital stays, and improvement in skin and gum health.
Of the pts studied, ranging in age from 5 months to 9 years, nine underwent treatment with RP-L201 and were observed for a period between 12 and 24 months. The dosage for RP-L201 varied, containing anywhere from 2.8×106 to 10×106 CD34+ cells/kg, and had a vector copy number (VCN) between 1.8 and 3.8. All pts showed restored PMN CD18 levels, with an average expression of 56.3%. Stable genetic markers were also observed, with an average VCN of 1.53 in peripheral blood mononuclear cells. A year post-treatment, the survival rate was a complete 100%, according to Kaplan-Meier analysis. There was a notable improvement from the initial high white blood cell count. Post-treatment, there was a marked decrease in both hospital stays and severe infections. There were no significant negative side effects directly linked to RP-L201. Analysis of the insertion sites revealed diverse integration patterns throughout the group.
The study reported that RP-L201 showed safety and effectiveness, correcting the LAD-I condition and improving the health of all nine pediatric pts in the study, as evidenced by clinical and lab results.
Source: https://ebmt2023.abstractserver.com/program/#/details/presentations/1822
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03812263
Kohn, D., Sevilla, J., Rao, G., Lopez, M.C., Almarza, E., Terrazas, D., Zubicaray, J., González-Vicent, M., Chetty, K., O’Toole, G., Xu-Bayford, J., Nicoletti, E., Fernandes, A., Kuo, C., Oliveira, S.D., Moore, T.B., Choi, G., Zeini, M., Mesa-Núñez, C., Thrasher, A., Bueren, J., Schwartz, J., Booth, C. Paed4-02 LENTIVIRAL-MEDIATED EX-VIVO GENE THERAPY FOR PEDIATRIC PATIENTS WITH SEVERE LEUKOCYTE ADHESION DEFICIENCY-I (LAD-I): INTERIM RESULTS FROM AN ONGOING PHASE 1/2 STUDY.
