CLL2-BIG: sequential treatment with bendamustine, ibrutinib and obinutuzumab (GA101) in chronic lymphocytic leukemia.

Autor: von Tresckow J; Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study Group, University of Cologne, Cologne, Germany. julia.von-tresckow@uk-koeln.de., Cramer P; Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study Group, University of Cologne, Cologne, Germany., Bahlo J; Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study Group, University of Cologne, Cologne, Germany., Robrecht S; Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study Group, University of Cologne, Cologne, Germany., Langerbeins P; Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study Group, University of Cologne, Cologne, Germany., Fink AM; Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study Group, University of Cologne, Cologne, Germany., Al-Sawaf O; Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study Group, University of Cologne, Cologne, Germany., Illmer T; BAG Freiberg-Richter, Jacobasch, Wolf, Illmer, Dresden, Germany., Klaproth H; Hämatologische/ Onkologische Praxis Dr. Klaproth, Neunkirchen, Germany., Estenfelder S; Department of Internal Medicine III, Ulm University, Ulm, Germany., Ritgen M; Department of Medicine II, University of Schleswig-Holstein, Kiel, Germany., Fischer K; Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study Group, University of Cologne, Cologne, Germany., Wendtner CM; Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study Group, University of Cologne, Cologne, Germany.; Department of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical Medicine, Hospital Munich-Schwabing, Munich, Germany., Kreuzer KA; Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study Group, University of Cologne, Cologne, Germany., Stilgenbauer S; Department of Internal Medicine III, Ulm University, Ulm, Germany.; Department of Internal Medicine I, Saarland University, Homburg, Germany., Böttcher S; Clinic for Internal Medicine III, Universityhospital Rostock, Rostock, Germany., Eichhorst BF; Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study Group, University of Cologne, Cologne, Germany., Hallek M; Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, CECAD Cluster of Excellence at the University of Cologne, Clinical Research Unit (KFO) 286, German CLL Study Group, University of Cologne, Cologne, Germany.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2019 May; Vol. 33 (5), pp. 1161-1172. Date of Electronic Publication: 2018 Dec 19.
DOI: 10.1038/s41375-018-0313-8
Abstrakt: Obinutuzumab (GA101) and ibrutinib show excellent efficacy for treatment of chronic lymphocytic leukemia (CLL). Preclinical investigations and a complementary safety profile were in support of testing their combined use. The exploratory CLL2-BIG-trial evaluated a sequential combination therapy following a recently proposed strategy. Two courses of bendamustine were used for debulking in patients with a high tumor load, followed by six courses of induction therapy with ibrutinib and GA101, followed by an MRD-triggered maintenance phase. The results of a pre-planned analysis at the end of the induction phase are presented. 61 patients were included, 30 previously untreated and 31 with relapsed/refractory CLL. 44 patients received bendamustine. During induction, neutropenia (14.8%) and thrombocytopenia (13.1%) were the most common CTC grade 3 and 4 events. One fatality (duodenitis) occurred. The overall response rate was 100%. 54.1% of patients achieved a partial remission, 41% a clinical complete remission (cCR) without confirmation by CT scan or bone marrow (BM) biopsy according to protocol and 4.9% a cCR with incomplete recovery of the BM. 29 patients (47.5%) had no detectable (<10 -4 ) minimal residual disease assessed by flow cytometry in peripheral blood. In conclusion, the BIG regimen is a safe and highly effective therapy for CLL.
Databáze: MEDLINE
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