High remission rates for new CLL treatment
Prof John Seymour - Peter MacCallum Cancer Centre, Victoria, Australia
Can you tell me a bit about your research in CLL?
Yes, here at the meeting the research we’re presenting is largely related to the programme of development of a drug now called venetoclax, previously ABT-199, a targeted drug developed by AbbVie and Genentech specifically inhibiting one of the proteins in the apoptotic pathway, Bcl-2. The data presented here is with the combination together with the rituximab that’s showing a very high response rate, approximately 80%. To me, the most exciting data is that we’re seeing a high proportion of complete remissions, 43% complete remissions, and really unprecedented in the context of heavily pre-treated and relapsed and refractory disease, nearly 50% of those responding patients have no detectable minimal residual disease by flow cytometry. So really very high quality responses and now with the follow-up improving we’re seeing that the majority of those are durable. So an effective drug, some issues with deliverability around initial cytopenias, particularly neutropenia in the first few months that does need to be managed, and previously a concern about tumour lysis syndrome but with a stepwise weekly dose escalation schedule that appears to have been mitigated. So very encouraging data with yet another new agent complimenting the spectrum of other highly targeted agents that we’re also seeing mature data presented here at the meeting from.
And what research do you have planned into the future?
A number of areas, as you see from the meeting a very exciting domain and a number of drugs that work in distinctly different ways. The research that we’re moving forward with is really in two areas, the first is using preclinical data to what we hope are rational combinations of these novel agents and the first that we’re moving forward with is a combination of ibrutinib together with venetoclax. The second is that some of our laboratory colleagues, particularly the lab of Sarah Jane Dawson, has developed a very specific and very highly sensitive PCR based assay that can be applied to the peripheral blood of patients that detects tumour specific mutations and appears to be a very sensitive marker of tumour burden that may obviate the need for bone marrow biopsies but also begins to inform some of the dynamics of clonal evolution. The Boston group presented some stunning data today on the mutational profile and the spectrum of molecular abnormalities and this circulating tumour DNA assay has the ability to monitor those dynamics in the blood of patients undergoing treatment. So they’re the two areas that our group is focussing on.
I know you’ve been one of the organisers of the conference and I was wondering if there were any highlights you’ve seen presented here that you’d like to talk about.
I’ve played a very small role; Stephen Mulligan has done the vast majority of the organising. I think the highlights have been many-fold. As I mentioned, from Dr Wu at Boston enhancing the genomic profile of the driver mutations here. The second in the clinical domain is really maturing data with the four classes or four types of drugs, newer drugs, we have – second generation anti-CD20 antibody obinutuzumab, mature ibrutinib data, particularly in the context of deletion 17p showing, I think, very high response rates and impressive durability but unclear around genomic instability and the potential for resistance to emerge. Also the PI3 kinase inhibitors, again highly efficacious, with maturing data some concerns around toxicity profile there that will need to be managed and monitored. For me they have really been the highlights of the meeting.
