Lymphoma: can PD-1 inhibition leverage ibrutinib's effect on T cells?

  • Herrera AF & al.
  • Am J Hematol
  • 17 Oct 2019

  • curated by David Reilly
  • Univadis Clinical Summaries
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Takeaway

  • In patients with relapsed/refractory follicular lymphoma (R/R FL), R/R germinal center B-cell diffuse large B-cell lymphoma (GCB DLBCL), or R/R non-GCB DLBCL, the addition of durvalumab to ibrutinib failed to meaningfully increase efficacy.

Why this matters

  • Ibrutinib is known to increase cytotoxic T-cell activation and to enhance proinflammatory cytokine secretion; such effects should theoretically work synergistically with programmed death cell-1 (PD-1) inhibition.

Study design

  • Phase 2 study to investigate ibrutinib+durvalumab in patients with R/R FL (n=27), R/R GCB DLBCL (n=17), non-GCB DLBCL (n=16), or unspecified DLBCL (n=2).
  • Median patient age, 60 (range, 22-82) years.
  • Funding: Pharmacyclics LLC, an AbbVie Company.

Key results

  • Overall response rate (ORR):
    • R/R FL: 26% (95% CI, 11%-46%).
    • GCB DLBCL: 13% (95% CI, 2%-38%).
    • Non-GCB DLBCL: 38% (95% CI, 15%-65%).
  • Median PFS:
    • R/R FL: 10.2 months.
    • GCB DLBCL: 2.9 months.
    • Non-GCB DLBCL: 4.1 months.
  • Median OS:
    • R/R FL: not evaluable.
    • GCB DLBCL: 5.5 months.
    • Non-GCB DLBCL: 7.3 months.
  • 56% of patients overall experienced grade 3-4 adverse events (AEs).
  • Most common grade 3-4 treatment-emergent AEs included neutropenia (21%) and dyspnea (10%).

Limitations

  • Open-label study design.