John N. Allan, MD, an assistant attending physician at NewYork-Presbyterian Hospital and an assistant professor of medicine at Weill Cornell Medical College of Cornell University, discusses a pooled analysis of 4 clinical trials with 4-year follow-up of first-line ibrutinib (Imbruvica) in patients with chronic lymphocytic leukemia (CLL) and TP53 aberration deletion 17p or a TP53 mutation.
The main outcomes being investigated in the analysis were progression-free survival (PFS), overall survival (OS), response rate, and safety. All 89 patients had TP53 disruption, a median age of 65 years, and 69% had unmutated IGHV. They all had fluorescence in situ hybridization analysis available, which showed that 53% of the patients had deletion 17p. Not all patients had sequencing available, but they found that 58 of the 89 subjects had sequencing results available and of those, 91% patients were positive for the mutation and were included in this study, according to Allan. The median follow-up was for 15 months on ibrutinib.
The ILLUMINATE (NCT02264574)and the EGOG1912 (NCT02048813)trials incorporated Ibrutinib plus either rituximab (Rituxan) or obinutuzumab (Gazyva). Allan says it was a mixed population in terms of the ibrutinib-based therapy; the other studies were using monotherapy only. Approximately half of the patients were treated with monotherapy and half were treated with anti-CD20 therapy.
The long-term outcome of 4-year PFS rate was 79% and the 4-year OS rate was 88%. Allan feels the results were impressive and showed that while these patients historically have done very poorly, they appear to be doing pretty well and overcoming some of this high-risk features of their disease biology.