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Leukemia. 2019 May;33(5):1161-1172. doi: 10.1038/s41375-018-0313-8. Epub 2018 Dec 19.

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

Author information

1
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.
2
Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study Group, University of Cologne, Cologne, Germany.
3
BAG Freiberg-Richter, Jacobasch, Wolf, Illmer, Dresden, Germany.
4
Hämatologische/ Onkologische Praxis Dr. Klaproth, Neunkirchen, Germany.
5
Department of Internal Medicine III, Ulm University, Ulm, Germany.
6
Department of Medicine II, University of Schleswig-Holstein, Kiel, Germany.
7
Department of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical Medicine, Hospital Munich-Schwabing, Munich, Germany.
8
Department of Internal Medicine I, Saarland University, Homburg, Germany.
9
Clinic for Internal Medicine III, Universityhospital Rostock, Rostock, Germany.
10
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.

Abstract

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.

PMID:
30568174
DOI:
10.1038/s41375-018-0313-8

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