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

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.

• Authors: Julia von Tresckow, Paula Cramer, Jasmin Bahlo, Sandra Robrecht, Petra Langerbeins, Anna-Maria Fink, Othman Al-Sawaf, Thomas Illmer, Holger Klaproth, Sven Estenfelder, Matthias Ritgen, Kirsten Fischer, Clemens-Martin Wendtner, Karl-Anton Kreuzer, Stephan Stilgenbauer, Sebastian Böttcher, Barbara F Eichhorst, Michael Hallek
• Journal: Leukemia (Leukemia) Vol. 33 Issue 5 Pg. 1161-1172 (05 2019) ISSN: 1476-5551 [Electronic] England
• PMID: 30568174 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Biomarkers
• Piperidines
• Pyrazoles
• Pyrimidines
• ibrutinib
• Bendamustine Hydrochloride
• Adenine
• obinutuzumab

Topics

• Adenine (analogs & derivatives)
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Bendamustine Hydrochloride (administration & dosage)
• Biomarkers
• Bone Marrow (pathology)
• Female
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell (diagnosis, drug therapy, mortality)
• Male
• Middle Aged
• Piperidines
• Pyrazoles (administration & dosage)
• Pyrimidines (administration & dosage)
• Remission Induction
• Survival Analysis
• Tomography, X-Ray Computed
• Treatment Outcome