Treatment Options for Older Patients With CLL

Steven Coutre, MD: We often treat older patients with ibrutinib. We’ve certainly treated them in the context of the trials, and we’ve treated those patients with commercially available ibrutinib, now that it’s approved as frontline. So, a very typical patient would be one that I saw last week; for example, a 78-year-old woman who I had been following for a number of years who presented initially with an asymptomatic lymphocytosis, and over the years has had some increase in her lymphocyte count. She’s developed some adenopathy as well as anemia, and now it’s gotten to the point where she’s significantly anemic and it’s impacting her quality of life. She’s symptomatic, so she really meets the standard need for treatment, and, of course, she’s 78. She made it very clear that she’s not interested in losing her hair, and she also didn’t like the idea of chemotherapy. It’s a good example of really looking at your individual patient and then deciding what your goal is. What do you want to accomplish when you’re choosing a treatment in that particular patient? So, it’s not just a one-size-fits-all. It’s not that I treat everyone with this regimen as initial treatment. You always look at your options, and then make a decision. And so, for her, it was rather easy. We have an oral therapy. It’s approved. It’s well tolerated. We know it’s going to work. And so, we can use that option and really reassure the patient that not only are we going to see a response, not only is she going to feel better because we’re effectively treating the disease, but she’s likely to tolerate it very well.

In an academic center, we’re often referred younger patients. So, it’s not perhaps your typical older patient, but somebody who’s quite young for their disease. I’ve actually seen patients, as young as in their 20s, believe it or not. But, a more typical patient might be somebody in their late 50s who is diagnosed and often doesn’t need treatment initially, but eventually will come to treatment, and they’re still young. Of course, people can have significant comorbidities. In the trials, that’s measured by what we call the Cumulative Illness Rating score, the CIR score, which I’m not a big believer in. It’s pretty easy to determine whether somebody is truly fit for a chemoimmunotherapy regimen or not. Do they have poorly controlled hypertension? Are they overweight? Do they have diabetes? You add up those risk factors, and it’s pretty easy to decide whether you’re thrilled about giving somebody a more intensive regimen; one which might cause neutropenia, lead to infections, for example. So, there isn’t anything really objective that I add up to make that decision.

The other factor that can play a role here, too, is renal function. A lot of our standard drugs are renally cleared. And so, for those with chronic kidney disease, one has to be particularly careful about who they’re giving some of our chemotherapy drugs to. Because, they’d be more prone to myelosuppression, and, therefore, more prone to infections.

For a younger, unfit patient, a drug like ibrutinib would be a very good option, as well for focusing on the tolerability, the safety aspect. So, you’re confident that you’re going to be able to deliver the therapy in that patient without having to interrupt because of complications, and, therefore, you’re confident you’re going to get the full therapeutic benefit. Of course, in the trials, including the RESONATE-2 trial, we weren’t treating patients under 65. But, since it’s commercially available and in other trials that are ongoing, we have done that. For example, in a large national trial, patients under the age of 70 have CR (cyclophosphamide/rituximab) versus ibrutinib plus rituximab. That trial has accrued over 500 patients. It’s fully accrued. We’ve treated patients on that trial, so we’ll wait and see what that shows.

CLL, as you remember, is a disease in older patients for the most part. The average patient is over 70 at diagnosis. The average patient doesn’t need treatment initially, so, of course, the average patient is well into their 70s before they start any treatment. Certainly, the use of stem-cell transplant is largely off the table there. But, we have younger patients, and so the issue of transplant often comes up in these patients. Should they be transplanted after their initial therapy? Are there certain subgroups like the deletion 17p where we should consider that? And I think it remains an open question. I think the pendulum has swung a bit with our newer therapies that are so effective and so well tolerated that we don’t have as great an urgency to consider transplant. Certainly, the results we’re seeing with deletion 17p with drugs like ibrutinib really allow us some breathing room. We also have new technologies coming along, CAR-T cells. So, nontransplant approaches, approaches that are hopefully less toxic and potentially curative. From my perspective, my motivation is to put transplanters out of business. We’ll see how things develop as we continue to develop these newer drugs.