Insights From: Naval G. Daver, MD, MD Anderson Cancer Center; Anthony Mato, MD, MSCE, Memorial Sloan Kettering Center
Anthony Mato, MD, MSCE: ASCO [The American Society of Clinical Oncology Annual Meeting] was a really exciting meeting this year. There were several important abstracts that were presented. I already went through CLL14, which is probably the most important practice-changing abstract that was presented at the meeting. Other things that I thought were interesting were that we had some preliminary data for the combination of obinutuzumab plus acalabrutinib as a first therapy: small number of patients, relatively small number of sites, but looked to be quite active with a high rate of response and deeper responses that we might see with a BTK inhibitor alone. The limitation of these studies, and I think hopefully it will be addressed in the future, is that these all continuous therapies. For example, the 1 that I just mentioned. And the hope will be that with the deeper responses, we may be able strategies to stop those combinations as well in appropriate patients.
There were additional data published at the meeting looking at CAR-T [chimeric antigen receptor T-cell therapy], specifically in relapsed-refractory CLL. A small number of patients and very highly selected centers. But again, CAR-T is something that’s active and may be a future available option for ultrarefractory patients.
I think 1 of the limitations of the data presented so far is that we have information about response rate, early responses, and depth of response but not a lot of information about durability of response and management of patients following CAR-T.
I think 1 of the more important abstracts presented at the meeting are the final analysis with 6-year follow-up of the RESONATE trial. This was a classic landmark investigation, which compared ibrutinib in the relapsed-refractory setting to the antibody ofatumumab. It was positive and helped to lead to the approval of ibrutinib in the relapsed-refractory setting. But now we have information about long-term follow-up, median progression-free survival of about 44 months, and then an expanded window into what the AE [adverse effect] profile of ibrutinib looks like in that setting; the maintenance of the advantage in terms of progression-free and overall survival.
So it’s very nice to see that studies that led to the approvals of these drugs are now reporting on longer term follow-up. It really helps us speak to informed consent with our patients, because with early follow-up—12 months, for example—there’s not a lot you can say. When you start to have 5-, 6-, 7-year follow-up, we can really give patients a window into how well the drugs are working, what toxicities are expected short and long term, and hopefully in the future of potential next therapies to rescue them from discontinuations.