Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: a phase 2, single-arm trial - 30/01/15
Summary |
Background |
Patients with chronic lymphocytic leukaemia (CLL) with TP53 aberrations respond poorly to first-line chemoimmunotherapy, resulting in early relapse and short survival. We investigated the safety and activity of ibrutinib in previously untreated and relapsed or refractory CLL with TP53 aberrations.
Methods |
In this investigator-initiated, single-arm phase 2 study, we enrolled eligible adult patients with active CLL with TP53 aberrations at the National Institutes of Health Clinical Center (Bethesda, MD, USA). Patients received 28-day cycles of ibrutinib 420 mg orally once daily until disease progression or the occurrence of limiting toxicities. The primary endpoint was overall response to treatment at 24 weeks in all evaluable patients. This study is registered with ClinicalTrials.gov, number NCT01500733, and is fully enrolled.
Findings |
Between Dec 22, 2011, and Jan 2, 2014, we enrolled 51 patients; 47 had CLL with deletion 17p13.1 and four carried a TP53 mutation in the absence of deletion 17p13.1. All patients had active disease requiring therapy. 35 enrolled patients had previously untreated CLL and 16 had relapsed or refractory disease. Median follow-up was 24 months (IQR 12·9–27·0). 33 previously untreated patients and 15 patients with relapsed or refractory CLL were evaluable for response at 24 weeks. 32 (97%; 95% CI 86–100) of 33 previously untreated patients achieved an objective response, including partial response in 18 patients (55%) and partial response with lymphocytosis in 14 (42%). One patient had progressive disease at 0·4 months. 12 (80%; 95% CI 52–96) of the 15 patients with relapsed or refractory CLL had an objective response: six (40%) achieved a partial response and six (40%) a partial response with lymphocytosis; the remaining three (20%) patients had stable disease. Grade 3 or worse treatment-related adverse events were neutropenia in 12 (24%) patients (grade 4 in one [2%] patient), anaemia in seven (14%) patients, and thrombocytopenia in five (10%) patients (grade 4 in one [2%] patient). Grade 3 pneumonia occurred in three (6%) patients, and grade 3 rash in one (2%) patient.
Interpretation |
The activity and safety profile of single-agent ibrutinib in CLL with TP53 aberrations is encouraging and supports its consideration as a novel treatment option for patients with this high-risk disease in both first-line and second-line settings.
Funding |
Intramural Research Program of the National Heart, Lung, and Blood Institute and the National Cancer Institute, Danish Cancer Society, Novo Nordisk Foundation, National Institutes of Health Medical Research Scholars Program, and Pharmacyclics Inc.
Le texte complet de cet article est disponible en PDF.Plan
Vol 16 - N° 2
P. 169-176 - février 2015 Retour au numéro
Article précédent
- Disease-free survival after complete mesocolic excision compared with conventional colon cancer surgery: a retrospective, population-based study
- Claus Anders Bertelsen, Anders Ulrich Neuenschwander, Jens Erik Jansen, Michael Wilhelmsen, Anders Kirkegaard-Klitbo, Jutaka Reilin Tenma, Birgitte Bols, Peter Ingeholm, Leif Ahrenst Rasmussen, Lars Vedel Jepsen, Else Refsgaard Iversen, Bent Kristensen, Ismail Gögenur, on the behalf of the Danish Colorectal Cancer Group
- Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial
- Anish Thomas, Arun Rajan, Arlene Berman, Yusuke Tomita, Christina Brzezniak, Min-Jung Lee, Sunmin Lee, Alexander Ling, Aaron J Spittler, Corey A Carter, Udayan Guha, Yisong Wang, Eva Szabo, Paul Meltzer, Seth M Steinberg, Jane B Trepel, Patrick J Loehrer, Giuseppe Giaccone
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?