Ibrutinib in Relapsed or Refractory Follicular Lymphoma


Key Points

  • Objective response was observed in 21% of patients.
  • Median duration of response was 19.4 months.

In the phase II DAWN study reported in the Journal of Clinical Oncology, Gopal et al found that ibrutinib (Imbruvica) produced a response in a minority of patients with relapsed or refractory follicular lymphoma.

Study Details

In the study, 110 patients with ≥ 2 prior lines of treatment (median = 3) received ibrutinib at 560 mg daily until progressive disease or unacceptable toxicity. The primary endpoint was independent review committee–assessed overall response rate; the endpoint was considered to be met if the lower bound of the 95% confidence interval (CI) was ≥ 18%. 

The median follow-up was 27.7 months. An objective response was achieved in 23 patients (20.9%, 95% CI = 13.7%–29.7%), failing to meet the lower-bound threshold for the primary endpoint. A complete response was observed in 12 patients (11%). The median duration of response was 19.4 months (range = 1 to ≥ 33 months). The median progression-free survival was 4.6 months; the overall survival rate at 30 months was 61%.

Exploratory analyses of T-cell subsets in peripheral blood and cytokines/chemokines in available samples showed that responders had downregulation of regulatory T cells (P = .02) and upregulation of the Th1-promoting (antitumor) cytokines interferon-gamma and interleukin-12 (P ≤ .035).

Safety Profile

Grade ≥ 3 adverse events occurred in 62% of patients, with the most common being neutropenia (14%), anemia (9%), and pneumonia (6%). Serious adverse events occurred in 48%, with the most common being pneumonia (6%), pyrexia (6%), pleural effusion (4%), sepsis (3%), atrial fibrillation (3%), and diarrhea (3%).

The investigators concluded, “With an [objective response rate] of 20.9%, ibrutinib failed to meet its primary efficacy endpoint in chemoimmunotherapy in patients with relapsed/refractory [follicular lymphoma], although responses were durable and associated with a reduction in regulatory T cells and increases in proinflammatory cytokines.”

The study was supported by Janssen Research & Development.

Ajay K. Gopal, MD, of the Seattle Cancer Care Alliance, Fred Hutchinson Cancer Research Center, is the corresponding author for the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.