Ibrutinib in combination with rituximab in relapsed or refractory mantle cell lymphoma: a single-centre, open-label, phase 2 trial - 24/12/15
, Hun Lee, MD a, Hubert Chuang, MD c, Nicolaus Wagner-Bartak, MD d, Frederick Hagemeister, ProfMD a, Jason Westin, MD a, Luis Fayad, MD a, Felipe Samaniego, MD a, Francesco Turturro, ProfMD a, Yasuhiro Oki, MD a, Wendy Chen, PA a, Maria Badillo, MSN a, Krystle Nomie, PhD a, Maria DeLa Rosa, BS a, Donglu Zhao, MD a, Laura Lam, PhD a, Alicia Addison, MS a, Hui Zhang, BSN a, Ken H Young, MD e, Shaoying Li, MD e, David Santos, MD f, L Jeffrey Medeiros, ProfMD e, Richard Champlin, ProfMD b, Jorge Romaguera, ProfMD a, Leo Zhang, MD aSummary |
Background |
Ibrutinib is approved in the EU, USA, and other countries for patients with mantle cell lymphoma who received one previous therapy. In a previous phase 2 study with single-agent ibrutinib, the proportion of patients who achieved an objective response was 68%; 38 (34%) of 111 patients had transient lymphocytosis. We hypothesised that adding rituximab could target mantle cell lymphoma cells associated with redistribution lymphocytosis, leading to more potent antitumour activity.
Methods |
Patients with a confirmed mantle cell lymphoma diagnosis (based on CD20-positive and cyclin D1-positive cells in tissue biopsy specimens), no upper limit on the number of previous treatments received, and an Eastern Cooperative Oncology Group performance status score of 2 or less were enrolled in this single-centre, open-label, phase 2 study. Patients received continuous oral ibrutinib (560 mg) daily until progessive disease or unacceptable toxic effects. Rituximab 375 mg/m2 was given intravenously once per week for 4 weeks during cycle 1, then on day 1 of cycles 3–8, and thereafter once every other cycle up to 2 years. The primary endpoint was the proportion of patients who achieved an objective response in the intention-to-treat population and safety assessed in the as-treated population. The study is registered with ClinicalTrials.gov, number NCT01880567, and is still ongoing, but no longer accruing patients.
Findings |
Between July 15, 2013, and June 30, 2014, 50 patients were enrolled. Median age was 67 years (range 45–86), and the median number of previous regimens was three (range 1–9). At a median follow-up of 16·5 months (IQR 12·09–19·28), 44 (88%, 95% CI 75·7–95·5) patients achieved an objective response, with 22 (44%, 30·0–58·7) patients achieving a complete response, and 22 (44%, 30·0–58·7) a partial response. The only grade 3 adverse event in >=10% of patients was atrial fibrillation, which was noted in six (12%) patients. Grade 4 diarrhoea and neutropenia occurred in one patient each. Adverse events led to discontinuation of therapy in five (10%) patients (atrial fibrillation in three [6%] patients, liver infection in one [2%], and bleeding in one [2%]). Two patients died while on-study from cardiac arrest and septic shock; the latter was deemed possibly related to treatment.
Interpretation |
Ibrutinib combined with rituximab is active and well tolerated in patients with relapsed or refractory mantle cell lymphoma. Our results provide preliminary evidence for the activity of this combination in clinical practice. A phase 3 trial is warranted for more definitive data.
Funding |
Pharmacyclics LLC, an AbbVie Company.
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Vol 17 - N° 1
P. 48-56 - janvier 2016 Retour au numéro
Article précédent
- Cancer drugs in 16 European countries, Australia, and New Zealand: a cross-country price comparison study
- Sabine Vogler, Agnes Vitry, Zaheer-Ud-Din Babar
- Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open-label, non-inferiority phase 3 trial
- Mathias Rummel, Ulrich Kaiser, Christina Balser, Martina Stauch, Wolfram Brugger, Manfred Welslau, Norbert Niederle, Christoph Losem, Hans-Peter Boeck, Eckhart Weidmann, Ulrich von Gruenhagen, Lothar Mueller, Michael Sandherr, Lars Hahn, Julia Vereshchagina, Frank Kauff, Wolfgang Blau, Axel Hinke, Juergen Barth, Study group indolent Lymphomas (StiL) †
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