Ibrutinib combined with venetoclax for the treatment of relapsed/refractory diffuse large B cell lymphoma.

Abstract

Treatment outcomes of relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) are far from satisfactory. Certain efficacy of ibrutinib has been observed in non-GCB subtype DLBCL patients. This study aimed to investigate the efficacy and safety of ibrutinib plus BCL2 inhibitor venetoclax in R/R DLBCL patients with non-GCB subtype and BCL2 overexpression. Combinational therapy (ibrutinib 560mg/day; venetoclax started 1 week later, oral dose increased from 100 to 400mg/day in 3 weeks) was conducted, and one cycle was 4 weeks. Both drugs were stopped when disease progress or serious adverse reactions appear. The primary end-point was overall response rate (ORR) at two cycles. From December 2018 to July 2020, a total of 13 patients were treated with the combined therapy. Among them, eleven (84.6%) patients previously received at least two treatment regimens, eight (61.5%) patients were C-myc and BCL2 double expression. The ORR at two cycles was 61.5%, with 3 (23.1%) patients achieved complete remission (CR) and 5 (38.4%) patients achieved partial remission (PR). The ORR at four cycles and six cycles was 53.8% and 46.2%, respectively. The median duration of response was 11 months (range, 1.5-13.6 months). The median progression-free survival and overall survival were 5.6 months (range, 0.4-15.6) and 11.3 months (range, 2.8-17.2), respectively. The most common adverse event was grade 1/2 neutropenia (53.8%), and nonhematologic toxicities included Grade1/2 diarrhea (46.2%) and elevated liver enzymes (30.8%). Combined therapy of ibrutinib and venetoclax showed promising efficacy and synergistic effects in R/R DLBCL patients with non-GCB subtype and BCL2 overexpression, and the toxicities were well-tolerated.

• Authors: Zhiyuan Zhou, Lei Zhang, Xinhua Wang, Xin Li, Ling Li, Xiaorui Fu, Xudong Zhang, Zhaoming Li, Zhenchang Sun, Mingzhi Zhang
• Journal: Annals of hematology (Ann Hematol) Vol. 100 Issue 6 Pg. 1509-1516 (Jun 2021) ISSN: 1432-0584 [Electronic] Germany
• PMID: 33900450 (Publication Type: Journal Article)

Chemical References

• BCL2 protein, human
• Bridged Bicyclo Compounds, Heterocyclic
• Piperidines
• Proto-Oncogene Proteins c-bcl-2
• Sulfonamides
• ibrutinib
• Adenine
• venetoclax

Topics

• Adenine (adverse effects, analogs & derivatives, therapeutic use)
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Bridged Bicyclo Compounds, Heterocyclic (adverse effects, therapeutic use)
• Female
• Humans
• Lymphoma, Large B-Cell, Diffuse (drug therapy)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• Neutropenia (chemically induced)
• Piperidines (adverse effects, therapeutic use)
• Proto-Oncogene Proteins c-bcl-2 (antagonists & inhibitors)
• Sulfonamides (adverse effects, therapeutic use)
• Treatment Outcome