Phase I study of zoledronic acid combined with escalated doses of interleukine‐2 for early in vivo generation of Vγ9Vδ2 T ‐cells after haploidentical stem cell transplant with posttransplant cyclophosphamide - Archive ouverte HAL
Article Dans Une Revue American Journal of Hematology Année : 2024

Phase I study of zoledronic acid combined with escalated doses of interleukine‐2 for early in vivo generation of Vγ9Vδ2 T ‐cells after haploidentical stem cell transplant with posttransplant cyclophosphamide

Amandine Le Bourgeois
  • Fonction : Auteur
Pierre Peterlin
Alice Garnier
  • Fonction : Auteur
Marion Eveillard
Yannick Le Bris
Simon Bouzy
  • Fonction : Auteur
Benoît Tessoulin
Thomas Gastinne
  • Fonction : Auteur
Viviane Dubruille
  • Fonction : Auteur
Cyrille Touzeau
  • Fonction : Auteur
Béatrice Mahé
  • Fonction : Auteur
Nicolas Blin
  • Fonction : Auteur
Anne Lok
  • Fonction : Auteur
Sophie Vantyghem
  • Fonction : Auteur
Clara Sortais
  • Fonction : Auteur
Chloé Antier
  • Fonction : Auteur
Philippe Moreau

Résumé

Abstract The presence of donor Vγ9Vδ2 T‐cells after haploidentical hematopoietic stem cell transplant (h‐HSCT) has been associated with improved disease‐free survival. These cells kill tumor cells in a non‐MHC restricted manner, do not induce graft‐versus‐host disease (GVHD), and can be generated by stimulation with zoledronic acid (ZA) in combination with interleukin‐2 (IL‐2). This monocentric phase I, open‐label, dose‐escalating study (ClinicalTrials.gov: NCT03862833) aimed at evaluating the safety and possibility to generate Vγ9Vδ2 T‐cells early after h‐HSCT. It applied a standard 3 + 3 protocol to determine the maximum tolerated dose (MTD) of increasing low‐doses of IL‐2 (5 days [d] per week, 4 weeks) in combination with a single dose of ZA, starting both the first Monday after d + 15 posttransplant. Vγ9Vδ2 T‐cell monitoring was performed by multiparameter flow cytometry on blood samples and compared with a control cohort of h‐HSCT recipients. Twenty‐six patients were included between April 2019 and September 2022, 16 of whom being ultimately treated and seven being controls who received h‐HSCT only. At the three dose levels tested, 1, 0, and 1 dose‐limiting toxicities were observed. MTD was not reached. A significantly higher number of Vγ9Vδ2 T‐cells was observed during IL‐2 treatment compared with controls. In conclusion, early in vivo generation of Vγ9Vδ2 T‐cells is feasible after h‐HSCT by using a combination of ZA and repeated IL‐2 infusions. This study paves the way to a future phase 2 study, with the hope to document lesser posttransplant relapse with this particular adaptive immunotherapy.
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Dates et versions

hal-04591453 , version 1 (28-05-2024)

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Maxime Jullien, Thierry Guillaume, Amandine Le Bourgeois, Pierre Peterlin, Alice Garnier, et al.. Phase I study of zoledronic acid combined with escalated doses of interleukine‐2 for early in vivo generation of Vγ9Vδ2 T ‐cells after haploidentical stem cell transplant with posttransplant cyclophosphamide. American Journal of Hematology, 2024, 99 (3), pp.350-359. ⟨10.1002/ajh.27191⟩. ⟨hal-04591453⟩
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