Practical Advice on Shared Decision-Making

Jan A. Burger, MD, PhD: In terms of side effects, if we want to contrast chemoimmunotherapy with the novel agents, there is a big difference. The biggest difference is lack of myelotoxicity. When you do chemoimmunotherapy, you will cycle patients through neutropenia, oftentimes associated with infectious complications, and sometimes we have issues that patients don’t recover their blood counts well. Platelet counts, neutrophil counts, and anemia could be issues. One of the biggest advantages of the new agents is that they lack myelotoxicity. And patients who are anemic to start with typically improve their peripheral blood cell counts; not only red cells, but also platelets and neutrophil counts within the first 6 to 9 months. There might be a rare exception, which are patients who have a history of autoimmune complications. Those patients need to be monitored a little more closely because sometimes, as with other treatments, the kinase inhibitors can cause a brief flare of autoimmune complications. And then patients could become cytopenic when they stop, but that’s a rare exception.

Other side effects that should be maybe mentioned, besides the myelotoxicity, would be gastrointestinal side effects on the kinase inhibitors. With ibrutinib, we know that mild diarrhea is common. Up to 1 in 3 patients have mild symptoms, but it’s usually transient, doesn’t need any therapeutic intervention. With idelalisib, we’ve learned over the last years that early gastrointestinal side effects or hepatitis can be an issue. But this drug is, in a way, different. It can sometimes activate the immune system to cause autoimmune complications like hepatitis, pneumonitis, and colitis. Therefore, it’s currently not being developed in the frontline setting and is reserved for relapsed patients.

My recommendation for somebody who sees these patients in private practice would be to bring all the different therapeutic options to the table, to discuss with the patient what to expect with each of these treatments, and then also to take into consideration the risk factors. Then, develop a treatment plan that’s really best suited for the patient’s wishes and that’s also best suited for the disease and disease control. But I think what we’re trying to do with our patients is to develop goals. If somebody is over 70, the goal would be to preserve, as best as possible, quality of life. For some patients, that might be just taking an oral medication for probably many years. And if that oral agent is well tolerated, that’s an optimal solution. But other patients may just want to have a brief period of treatment and be done with treatment after 4 to 6 months. For those patients, for example, antibody-based treatment could be a good option.

Think about a younger patient who’s under 65, who has comorbidities, and who has relapsed disease after chemoimmunotherapy, which used to be the standard treatment for these younger patients. In that setting, we’ve used ibrutinib since about 2010. Many of these patients were resistant to fludarabine, for example, and those patients, in the first years, we really didn’t have good alternative. And it was a very excellent experience for these patients. Many of these patients continue on those extension studies. And those patients who have this past experience can really compare their side-effect profiles, can speak to the durability of their remission. So, it’s been a very positive experience in that patient group, as well. Are we going to see that as much in the future? I’m not sure how frequent chemoimmunotherapy is still going to be used in the next 10 years in these younger patients. Some patients come and see us. Even in frontline setting, they don’t want to go that route, but others do and we might still see those patients occasionally. For those patients, in my experience, ibrutinib has been a very good alternative. Some patients may not tolerate it and that’s sometimes reason to move elsewhere—but that’s a minority of patients. And many patients have very durable remissions.

Case 1:A Fit Elderly Patient with Newly-Diagnosed Chronic Lymphocytic Leukemia.