Gopal AK, et al. - Authors evaluated the effectiveness and safety of single-agent ibrutinib in chemoimmunotherapy in relapsed/refractory follicular lymphoma (FL) patients. In patients with relapsed/refractory FL, ibrutinib did not meet its primary efficacy endpoint as chemoimmunotherapy, nonetheless, they noted a durability and association of responses with a reduced regulatory T cells and increased proinflammatory cytokines.

Methods

• The DAWN study was an open-label, single-arm, phase II study of ibrutinib including patients with FL with two or more prior lines of therapy.
• Ibrutinib 560 mg daily was administered until progressive disease and/or unacceptable toxicity.
• Independent review committee-assessed overall response rate (ORR; complete response plus partial response) was the primary objective.
• Authors conducted exploratory analyses of T-cell subsets in peripheral blood (baseline/cycle 3) and cytokines/chemokines (baseline/cycle 2) for available samples.

Results

• As per data, between March 2013 and May 2016, 110 patients with a median of three prior lines of therapy were enrolled.
• Findings revealed that ORR was 20.9% (95% CI, 13.7% to 29.7%), which did not meet the 18% lower-bound threshold for the primary end point, at median follow-up of 27.7 months.
• A complete response was achieved by 12 patients (11%; 95% CI, 5.8% to 18.3%).
• Results demonstrated that 19.4 months (range, 1 to ≥ 33 months) was median duration of response, with a median progression-free survival of 4.6 months and a 30-month overall survival of 61% (95% CI, 0.51% to 0.70%).
• In 67%, lymphoma symptoms resolved.
• Data showed that, upon continuing therapy (pseudoprogression), response was seen in 7 of 32 patients who experienced initial radiologic progression.
• Diarrhea, fatigue, cough, and muscle spasms were the most common adverse events; 48.2% of patients reported serious adverse events.
• Regulatory T cells were downregulated at C3D1 (P=.02), and Th1-promoting (antitumor) cytokines interferon-γ and interleukin-12 increased (P ≤ .035) in patients who experienced a response.