Nitin Jain, MD, on Front-Line Therapies for CLL: Research Highlights From ASCO 2025

Today at ASCO 2025, there have been some important abstracts reported on chronic lymphocytic leukemia (CLL), and I would just focus on the frontline therapy of CLL, which is really seeing a lot of evolution over the course of the last few years. We are moving away completely from chemotherapy, and now increasingly we are using targeted therapies, and up until now the standard treatments have been to use a BTK inhibitor in a continuous fashion. There’s also data with venetoclax plus obinutuzumab for one-year therapy. But what’s happening in the field is, and we saw that from last year's meeting at ASH, that there’s a combination of acalabrutinib plus venetoclax with and without obinutuzumab also coming into the frontline setting in the context of CLL. At the ASCO meeting, we had a couple of abstracts which I would want to highlight. The first one is an update of the CAPTIVATE study. CAPTIVATE is a study where newly diagnosed patients who received treatment for CLL were given ibrutinib plus venetoclax for a duration of one year. And now what we saw in a poster session was up to five and five-and-a-half year follow-up of these patients, indicating the durability of remission for these patients with such a one-year therapy. I would say that the patients who are deletion 17p/TP53 are not doing as well with this one-year time-limited regimen, but other patients seem to be doing well long-term with this one-year regimen. Also, we heard data from the SEQUOIA trial, which is a combination of zanubrutinib plus venetoclax, and they reported data specifically in the context of TP53 patients, and they also show very high rates of MRD-negative remission and durable remission. With the strategy for patients with CLL moving forward, I would say that we are expecting at the EHA meeting coming soon some phase three studies coming out in the context of CLL for which the data is already public, which I think will be very informative as we kind of decide how the first-line therapy for patients with CLL is going to continue to evolve. And I would also say that there are some really exciting drugs in early development, all in phase one, phase two, and planned for phase three studies in CLL, with drugs called BTK degraders, drugs called bispecific antibodies, which already have publicly available data showing that they are working very well. And I think we and others are looking forward to how these drugs move into the early lines of therapy, including first-line therapy, in the next one to two years for patients with CLL.