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Impact of delayed CAR T-cell infusion on clinical outcomes in R/R LBCL

By Abhilasha Verma

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Feb 21, 2024

Learning objective: After reading this article, learners will be able to cite a new clinical development in lymphoma.


Below, we summarize a retrospective study published by Jallouk et al.1 in Haematologica on the impact of delay in cell infusion after lymphodepleting chemotherapy administration on clinical outcomes in patients with relapsed/refractory large B-cell lymphoma (LBCL).

Study design1

  • This was a retrospective study of patients with relapsed/refractory LBCL treated with standard-of-care axicabtagene ciloleucel (axi-cel).
  • Delayed cell infusion was defined as axi-cel infusion occurring 6 days after the initiation of lymphodepleting chemotherapy.
  • Key outcomes measured included overall response rate, progression-free survival (PFS), overall survival, cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS).

Key findings1

  • Overall, 240 patients were included:
    • 40 patients had a delay in axi-cel infusion, due to active infection (n = 34), need for disease-related procedures (n = 3), and logistical reasons (n = 3)
    • According to univariate analysis, patients with delayed cell infusion had lower absolute neutrophil count (p = 0.006), lower platelets (p = 0.004), lower hemoglobin (p < 0.001), and higher C-reactive protein (CRP) (p = 0.001) vs patients with on-time infusion
    • According to multivariate analysis, patients with delayed cell infusion had lower absolute neutrophil count (p = 0.025) and higher CRP (p = 0.037) than patients with on-time cell infusion
  • Patients with delayed infusion had a lower Day 30 overall response rate and complete response rate vs those with on-time infusion (Figure 1)

Figure 1. ORR and CR in patients with delayed infusion vs on-time infusion* 

CR, complete response; ORR, overall response rate; NS, not significant.
*Adapted from Jallouk, et al.1

 

    • With a median follow-up of 25.7 months, patients with delayed vs on-time infusion had significantly shorter median PFS (3.5 vs 8.2 months; p = 0.002) and overall survival rates (7.8 vs 26.4 months; p = 0.046)
    • Patients who experienced delays of 2–5 days and >5 days, but not 1 day, had significantly shorter median PFS (1.8 months and 4.6 months, respectively) than those who had on-time infusion (8.2 months)
    • The association between delayed infusion and shorter PFS was maintained on multivariate analysis including age, International Prognostic Index score, lactate dehydrogenase, and CRP
  • Patients with delayed cell infusion had similar rates of adverse effects vs those with on-time cell infusion
    • Any-grade CRS (90% vs 93.5%) and Grade 3–4 CRS (12.5% vs 8.0%)
    • Any-grade ICANS (65% vs 64.5%) and Grade 3–4 ICANS (42.5% vs 39.5%)
Key learnings
  • In this study, delay (particularly ≥2 days) in chimeric antigen receptor T-cell administration after initiating lymphodepleting chemotherapy was associated with poor outcomes in patients with LBCL.
  • This study suggests that reviewing factors associated with a delay in cell infusion is important and that careful consideration of whether to proceed with infusion or to further delay until the patient can receive another course of lymphodepleting chemotherapy may be required.
  • Further studies are needed to guide strategies to improve chimeric antigen receptor T-cell efficacy in this patient population.

References

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Large B-cell lymphomaAggressive B-cell lymphomas

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