TCT 2019—Combination of CAR-T therapy and ibrutinib may improve response in CLL


  • Tara Haelle
  • Univadis
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Takeaway

  • In patients with relapsed or refractory chronic lymphocytic leukemia (CLL), concurrently adding ibrutinib to CD19 chimeric antigen receptor T-cell (CAR-T) therapy may improve response and reduce toxicity.

Why this matters

  • CAR-T cell therapy has been effective in acute lymphocytic leukemia (ALL) and non-Hodgkin lymphoma (NHL) but less so in patients with CLL, who have poorer outcomes if refractory to ibrutinib. 

Study design

  • Phase 1/2 retrospective study compared outcomes among patients with CLL who received only CAR-T therapy (n=24) and a subsequent cohort who concurrently took ibrutinib with CAR-T therapy (n=19), all with persistent disease after ibrutinib therapy.
  • Funding: Juno Therapeutics/Celgene; Bezos Family; Integrated Immunotherapy Research Center; National Cancer Institute, Washington State; and University of British Columbia.

Key results

  • 32% of patients discontinued ibrutinib.
  • Any cytokine release syndrome (CRS) occurred in 74% taking ibrutinib and 92% not taking it (P=.21), but CRS severity (grade ≥3) was lower in the ibrutinib group (0% vs 25% without; P=.03).
  • Serum peak levels of cytokines linked to severe CRS were significantly lower in those taking ibrutinib (IL-6, P=.03; soluble TIM-3, P=.004; monocyte chemoattractant protein-1 [MCP-1], P<.001 soluble il-2 receptor alpha p tgf-beta>
  • 4 weeks after CAR-T cell infusion, 83% taking ibrutinib and 65% not had complete or partial response (P=.38).
  • In vivo CD4+ CAR-T cell expansion was significantly improved among patients taking ibrutinib (P=.03).
  • 1 patient taking ibrutinib developed grade 2 CRS and died following presumed ibrutinib-related cardiac arrhythmia. 

Limitations 

  • Several major findings did not reach significance.

Highlights vom TCT-Kongress 2019