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[Preprint]. 2024 Apr 11:rs.3.rs-4232549.
doi: 10.21203/rs.3.rs-4232549/v1.

Eighteen-year survival after GD2-directed Chimeric Antigen Receptor-Modified Immune Effector Cell Treatment for Neuroblastoma

Li Che-Hsing  1   2   3 , Sandhya Sharma  1 , Andras A Heczey  1   2   4 , David H M Steffin  1   4 , Chrystal U Louis  1 , Bambi J Grilley  1   4 , Sachin G Thakkar  1 , Mengfen Wu  4 , Tao Wang  4 , Cliona M Rooney  1   4 , Malcolm K Brenner  1   4 , Helen E Heslop  1   4
Affiliations

Eighteen-year survival after GD2-directed Chimeric Antigen Receptor-Modified Immune Effector Cell Treatment for Neuroblastoma

Li Che-Hsing et al. Res Sq. .

Update in

Abstract

We report long-term outcomes up to 18 years of a clinical trial treating children with neuroblastoma with EBV-specific T lymphocytes and CD3-activated T cells - each expressing a first-generation chimeric antigen receptor targeting GD2 with barcoded transgenes to allow tracking of each population. Of 11 patients with active disease at infusion, three patients achieved a complete response that was sustained in 2, one for 8 years until lost to follow up and one for 18+ years. Of eight patients with a history of relapse or at high risk of recurrence, five are disease-free at their last follow-up between 10-14 years post-infusion. Intermittent low levels of transgene were detected during the follow up period with significantly greater persistence in those who were long-term survivors. In conclusion, patients with relapsed/refractory neuroblastoma achieved long-term disease control after receiving GD2 CAR-T cell therapy including one patient now in remission of relapsed disease for >18 years.

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Conflict of interest statement

Competing interest statement HEH and MKB serve on the advisory board for March Biosciences. CMR, MKB and HEH are cofounders and equity holders in AlloVir Inc and Marker Therapeutics. MKB and CMR have equity in March Biosciences, and serve on advisory boards for Marker Therapeutics, Allogene, Walking Fish, Abintus, Tessa Therapeutics, Athenex, Onk Therapeutics, Coya Therapeutics, Triumvira, Adaptimmune, Vor Therapeutics, and Tscan. HEH has served on advisory boards for GSK, Fresh Wind Biotechnologies and Tessa Therapeutics and has share options in Co-Regen. BJG owns QBRegulatory Consulting, which has agreements with March Biosciences. CUL has equity and is an employee of Zentalis Pharmaceuticals. AAH has consultancy / scientific advisory roles with Waypoint Bio, Dispatch Bio and Cargo Therapeutics. The remaining authors declare no competing financial interests.

Figures

Extended Data Fig. 1.
Extended Data Fig. 1.
Graphical summary of the study design. NB, neuroblastoma.
Extended Data Fig. 2.
Extended Data Fig. 2.
Table summary of patients’ best response during the therapy.
Extended Data Fig. 3.
Extended Data Fig. 3.
Survival estimates for all patients (n=19). (A) EFS. (B) OS.
Fig. 1.
Fig. 1.
Long-term outcomes and T cell persistence after GD2 CAR-T infusions. (A) The EFS was defined from the date of first infusion to the date of disease relapsed or progressed, or last contact. (B) The OS was defined from the date of first infusion to the date of death with any causes or last contact. Log-rank test was used to compare the two groups. (C) The transgene levels (copy number/ 1 μg DNA) of both CAR-ATCs and CAR-VSTs in patients’ peripheral blood after infusion were measured by RT-qPCR and visualized using a heatmap. Each patient’s results (upper: CAR-VSTs; lower: CAR-ATCs) were presented in three categories: dark green, > 10 copy numbers; light green, 0 – 10 copy numbers; pink, undetectable. The gray color means there was no sample collected. (D) Difference in duration of detectable transgene between non-LTS and LTS. The median and range was demonstrated as the boxes. Three patients were excluded in the analysis (CAGT #1040 died shortly without providing accurate duration; #1089 and #1290 were lost to follow-up). Mann-Whitney U test was analyzed to compare the median in LTS and non-LTS.
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References

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