Initiation of Up-front Therapy for CLL

Steven Coutre, MD:The treatment of CLL is really undergoing a transformative period, largely because of these new oral agents. They’re really targeted therapies rather than traditional chemotherapy or chemoimmunotherapy. In the last several years, we’ve seen an acceleration of the development of these drugs and broader use of them.

In terms of up-front therapy, we’ll often break down patients into several groups, perhaps an older patient, a younger patient. Sometimes we also differentiate by fitness, meaning how well they might be able to tolerate a given therapy. One thing to keep in mind is that for CLL, the average patient at diagnosis is over 70, so I guess you’d call that older. For that typical patient, in the past, perhaps we might not consider as aggressive a treatment regimen. If patients were less fit, we would choose agents based on those criteria. Those boundaries are blurring a bit now because newer agents, drugs like ibrutinib, are very well tolerated. You could consider giving them to older patients, the patients who are less fit. There is nothing wrong with giving it to a younger patient who is fit either.

Our standard approach, traditionally for treating CLL, whether in the frontline setting or in the relapsed setting, has been chemotherapy or chemoimmunotherapy. Combination therapy has become much more relevant. The immunotherapy aspect is usually an antibody, like rituximab used in combination. For example, we have several very standard regimens: bendamustine and rituximab, and the FCR regimen (fludarabine/cyclophosphamide/rituximab). Those were often our choices. In older patients, single-agent therapy, like chlorambucil alone or maybe chlorambucil plus rituximab, can be used. We’ve had another antibody approved for use in CLL, obinutuzumab, and an older drug, ofatumumab. Different choices and how you combine those and how you sequence them is quite variable.

With newer oral agents that are extremely effective and also very well tolerated, we’re going to see that all change. Certainly, in the relapsed setting, in patients who’ve already had standard chemoimmunotherapy, there’s generally no reason not to use a drug like ibrutinib. If you repeat a regimen, a chemoimmunotherapy regimen, or give one that’s a little different, you often have fewer patients respond, and that response duration is shorter. You’re still going to be facing that issue down the road. Whereas with a drug like ibrutinib, right now we’re getting very prolonged responses and we may be able to continue to manage patients for many years with that approach. As we get more data in direct comparison to some of our chemoimmunotherapy regimens, we’ll see increasing use of ibrutinib.

Steven Coutre, MD, shares insights into his approach to frontline therapy for chronic lymphocytic leukemia