ERIC 2024 | The evolution of frontline treatment for CLL: from chemoimmunotherapy to targeted agents

So the transformation of CLL treatment has really been profound over the last 15 years or so. In particular, when we first saw the introduction of BTK inhibitors and PI3 kinase inhibitors, we had our first really targeted therapies for CLL, and it began this move away from chemoimmunotherapy, which was somewhat effective for certain types of CLL, but was particularly ineffective for high-risk CLL and more aggressive disease. So what we’ve seen really in the last few years now is we’ve had the approval of several of the targeted BTK inhibitors that are used in the frontline setting. It’s a very effective treat to progression type of strategy with more of a continuous treatment approach. But more recently, in the last five years or so, we’ve seen the development of time-limited combinations that are typically based on venetoclax therapy. So in particular, venetoclax plus obinutuzumab first, and more recently, venetoclax plus ibrutinib which is approved in certain countries. So really the whole field has changed for us. We very rarely use chemoimmunotherapy these days. For most patients who have access to targeted therapies this is going to be the best approach and we can be very successful even in patients with high genetic risk markers like TP53 aberration. So we’ve made a lot of progress but still a lot of improvements are needed particularly for those high-risk patients.