• Biomarker analysis of patients with follicular lymphoma treated with ibrutinib in the phase 2 DAWN study.

      Salles, G; Gopal, A; Schuster, S; Trotman, J; Hess, G; Hou, JZ; Yacoub, A; Lill, M; Martin, P; Vitolo, U; et al. (2017)
    • Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial.

      Horwitz, S; O'Connor, O; Pro, B; Illidge, Timothy M; Fanale, M; Advani, R; Bartlett, N; Christensen, J; Morschhauser, F; Domingo-Domenech, E; et al. (2019)
    • European phase II study of mogamulizumab, an anti-CCR4 monoclonal antibody, in relapsed/refractory peripheral T-cell lymphoma.

      Zinzani, P; Karlin, L; Radford, John A; Caballero, D; Fields, P; Chamuleau, M; D' Amore, F; Haioun, C; Thieblemont, C; González-Barca, E; et al. (2016-07-14)
    • Ibrutinib as treatment for patients with relapsed/refractory follicular lymphoma: results from the open-label, multicenter, phase II DAWN study.

      Gopal, A; Schuster, S; Fowler, N; Trotman, J; Hess, G; Hou, J; Yacoub, A; Lill, M; Martin, P; Vitolo, U; et al. (2018-05-31)
      Purpose The Bruton's tyrosine kinase inhibitor ibrutinib has demonstrated clinical activity in B-cell malignancies. The DAWN study assessed the efficacy and safety of single-agent ibrutinib in chemoimmunotherapy relapsed/refractory follicular lymphoma (FL) patients. Methods DAWN was an open-label, single-arm, phase II study of ibrutinib in patients with FL with two or more prior lines of therapy. Patients received ibrutinib 560 mg daily until progressive disease/unacceptable toxicity. The primary objective was independent review committee-assessed overall response rate (ORR; complete response plus partial response). Exploratory analyses of T-cell subsets in peripheral blood (baseline/cycle 3) and cytokines/chemokines (baseline/cycle 2) were performed for available samples. Results Between March 2013 and May 2016, 110 patients with a median of three prior lines of therapy were enrolled. At median follow-up of 27.7 months, 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). Twelve patients achieved a complete response (11%; 95% CI, 5.8% to 18.3%). Median duration of response was 19.4 months (range, 1 to ≥ 33 months), 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%). Lymphoma symptoms resolved in 67%. Seven of 32 patients who experienced initial radiologic progression responded upon continuing therapy (pseudoprogression). The most common adverse events were diarrhea, fatigue, cough, and muscle spasms; 48.2% of patients reported serious adverse events. In patients who experienced a response, regulatory T cells were downregulated at C3D1 ( P = .02), and Th1-promoting (antitumor) cytokines interferon-γ and interleukin-12 increased ( P ≤ .035). Conclusion With an ORR of 20.9%, ibrutinib failed to meet its primary efficacy end point in chemoimmunotherapy in patients with relapsed/refractory FL, although responses were durable and associated with a reduction in regulatory T cells and increases in proinflammatory cytokines.