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  3. Tumor burden-guided dosing contributes to mitigation of immunotoxicities following treatment with obecabtagene autoleucel in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia

Tumor burden-guided dosing contributes to mitigation of immunotoxicities following treatment with obecabtagene autoleucel in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia

Fecha de publicación:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Jabbour, E
  • Sandhu, KS
  • Shaughnessy, P
  • Logan, AC
  • Abedi, M
  • Shah, BD
  • Bishop, MR
  • Park, JH
  • DeAngelo, DJ
  • Tholouli, E
  • Yallop, D
  • Chaganti, S
  • Hodby, K
  • Barba, P
  • Menne, T
  • Shang, JS
  • Lao-Sirieix, P
  • Brugger, W
  • Roddie, C

Grupos

Abstract

Obecabtagene autoleucel (obe-cel) is a CD19-targeted autologous chimeric antigen receptor T-cell therapy (CAR T) with a fast off-rate binding domain, administered as split-dose infusions guided by pre-lymphodepletion tumor burden (low-tumor-burden [TB] group: <= 20%; high-TB group: >20% bone marrow [BM] blasts). Obe-cel treatment in adult relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) was investigated in the phase Ib/II FELIX trial. Here, we report pharmacokinetics, safety, and efficacy outcomes in patients with low or high tumor burden and discuss the evidence/rationale justifying the spilt-dose strategy and threshold used to classify the groups. Tumor burden at lymphodepletion was a critical driver of CAR T-cell expansion; a 50% increase, e.g., 70% versus 20% BM blasts, was associated with a 1.9-fold increase (95% confidence interval: 1.4-2.6) in maximal expansion of CAR T cells. Robust CAR T-cell expansion was observed in both tumor burden groups. The incidence of grade >= 3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome was minimal in both the low-and high-TB groups (2% vs. 3% and 4% vs. 9%, respectively). Although the overall remission rate was higher in the low-TB group (85%), it also remained high in the high-TB group (73%). Evidence from FELIX suggests that use of tumor burden--guided dosing may mitigate the typical effects of immunotoxicity while maintaining substantial efficacy. Although further study is needed to better characterize the effects of the split-dosing strategy, the clinical evidence supports its use when administering obe-cel for the treatment of R/R B-ALL.

Datos de la publicación

ISSN/ISSNe:
0390-6078, 1592-8721

HAEMATOLOGICA  FERRATA STORTI FOUNDATION

Tipo:
Article
Páginas:
1999-2010
PubMed:
41504229
Factor de Impacto:
2,528 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 1

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