Minimal Residual Disease Assessment in Lymphoid Malignancies - Episode 1

Goals of Therapy in CLL


Thomas J. Kipps, MD, PhD: When you talk to a patient and understand what they’re facing, it’s very important to try and define, what goals do we have with treatment and when is the most appropriate time to start treatment? Obviously, we’ve seen patients with CLL who are in their 20s. It’s not usual. The average age of onset is in the late 60s or early 70s. However, we see a full spectrum. And obviously, younger patients who can tolerate more intensive chemotherapy may be able to achieve a complete response, with eradication of the leukemia. This is attractive, because after having a course of therapy of 4 to 6 months, they may be free of their disease, put it in the rearview mirror, have improvements in their blood counts, and not have to deal with taking continuous therapy.

That’s attractive to some patients who are younger and fitter who do not have markers that would indicate they would have a poor response to chemotherapy. One of those is deletion in chromosome 17. So, obviously, if they have that, I would probably advise them to steer clear of a chemotherapy-based regimen.

There is a distinction between leukemia cells that have antibody genes that are mutated versus nonmutated. We know that for patients who have leukemia cells that have unmutated antibody genes, even if they have a stellar response, the disease may tend to recur within a few years after treatment. And you’d like to get good bang for your buck in going through the chemoimmunotherapy regimen. Those patients who have done very well with the chemoimmunotherapy regimen, being younger in age, typically have leukemia cells that have mutated antibody genes and have a lower amount of a protein called beta-2 microglobulin in their blood. So, those patients in particular seem to fair pretty well. And so, stratifying patients who receive a chemoimmunotherapy regimen who wish to put the disease in the rear-view mirror and go on with their lives without having to take continuous therapy—it’s a good choice.

Now, if a patient’s in their 80s or 90s, it may not be worth the consideration to try and get the disease so much into remission if they have to go through therapy that’s going to end their lives. And you have to be careful. We have to be mindful of limitations and how well patients can tolerate these regimens. As we get older, just like with our knees, we can’t play contact sports any more. We have to be mindful of age limitations and comorbidities that will influence our ability to take one therapy or the other.

The ability to take very intensive therapy will decline over time. Most of the patients may want to have their disease controlled so they can be with their grandkids and what have you. With the advent of these newer therapies, it’s possible to control the disease and to keep it at bay. It may not give us a complete response, where it allows us to stop therapy altogether; however, if the therapy is well tolerated and they are not having complications from their leukemia, that may be a favorable outcome for some patients. So, discuss that with patients to try and define what their objectives are with treatment. Even younger patients may opt for that, too, if they are not so inclined to try and get into what may be considered a home run with chemoimmunotherapy.

Transcript Edited for Clarity