Jonathon B. Cohen, MD, discusses the potential benefit of offering deferred therapy to asymptomatic patients with mantle cell lymphoma.
Jonathon B. Cohen, MD, associate professor of oncology and urology at Johns Hopkins Medicine
Jonathon B. Cohen, MD
Mantle cell lymphoma (MCL) is widely described as an aggressive disease for which there is no cure. However, there is a subset of patients with MCL who may benefit from deferred treatment after initial diagnosis, according to Jonathon B. Cohen, MD.
A retrospective analysis was conducted using comprehensive clinical data to evaluate the use of deferred therapy in newly diagnosed patients with MCL. This multicenter cohort analysis also examined safety data associated with patients who were given deferred treatment. Adult patients diagnosed with MCL between 1993 and 2015 from multiple sites were included, comprising a total of 395 patients.
Investigators reported that 72 (18%) patients received deferred therapy; these patients were more likely to have no B symptoms, an ECOG performance status of 0, and normal LDH levels. Deferred therapy did not result in significant changes in overall survival (OS; HR, 0.64; 95% CI, 0.22-1.84; P = .407).
In an interview with OncLive®, Cohen, assistant professor, Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute of Emory University, discussed the potential benefit of offering deferred therapy to asymptomatic patients with MCL.Cohen: Historically, MCL has been thought to have been an aggressive disease. In the past, the expected survival was only about 3 to 5 years. However, what we have found over the last several years is that there are some patients who present with MCL and have no symptoms and actually a very low burden of disease. In some instances, these are patients who have disease primarily in the bone marrow and the blood, and may not necessarily have a lot of disease in their lymph nodes.
One of the challenges we have had with the management of this disease is that, because it has historically behaved so aggressively, we feel everybody must get aggressive therapy upfront. Then there are these patients with lower-grade disease, clinically, and it just doesn't make sense to treat them so aggressively. Several years ago, there was a study published by the group from Weill Cornell Medicine by Dr Peter Martin, which looked at their own experience in observing patients with MCL who had no symptoms at the time of diagnosis. It appeared that those patients did just as well as patients who were treated right at the time of diagnosis. We did a larger study where we collected data from 5 centers instead of just 1, to try to assess the role of deferred therapy, and to determine whether it is a safe approach for patients with MCL.We found that a little less than one-fifth of all patients received deferred therapy. The way we defined this was by saying that any patient who did not initiate any sort of chemotherapy within 3 months of their diagnosis was felt to have been deferred. This means that those patients were purposefully not getting treated. Again, we found that in about 18% of patients.
Interestingly, we found that there was no significant impact on OS when we looked at those patients with deferred therapy versus those who received therapy immediately. In fact, it appears that patients who had deferred therapy may live a little bit longer, although it is important to interpret that with caution. This is because those are often patients with lower-risk disease to begin with, and that is how they were ultimately chosen to be deferred. It certainly did not appear to be unsafe; it is a very appropriate option for patients with asymptomatic disease.There has been some concern over whether it is safe to observe patients with MCL because historically, most patients had more aggressive disease. There have not been a lot of studies to support this type of an approach, so that is why this is important work. Hopefully with these types of findings, it will make physicians feel more comfortable incorporating this as a potential approach to the management of those patients.That may be one of the more difficult aspects of the entire process—explaining to a patient the rationale for taking such an approach to management. Certainly, it is unnerving for a patient who has been recently diagnosed with MCL to be told that told they will be observed instead of started on therapy.
What I would tell a patient is that we still feel that they will require treatment, and when they do, we will be prepared to give them the best possible therapy. MCL is not typically felt to be a curable disease, and our goal from the time that a patient is diagnosed is to do whatever we can for them to live as long as possible, and to be well for as long as possible. If that could include a period of time where they did not have to be on treatment, that is worth considering.
What I often tell patients who are asymptomatic is that it will be impossible for me to make them feel any better than they already do, because they don't have any symptoms. By starting patients on treatment, all I can really do is [not] make them feel worse. Even if they tolerate the therapy well, there are significant costs, doctor visits, side effects, and so forth. In general, if a patient can avoid all of that for a period of time, it can certainly be clinically meaningful.The key is that you have to remember that not all patients with MCL are the same. Historically, patients who were fit and young were offered aggressive therapy including transplant, whereas those who were unfit were offered less-aggressive therapy.
It is important to take into consideration the actual disease and how it is behaving in an individual patient, and to use that information to help guide decision-making. It is not just about the fitness of the patient and their ability to tolerate therapy, but whether their disease and its clinical behavior requires treatment.One other thing that has come out of this project is the question of what should be done with patients who defer therapy when the time comes for treatment. There are some additional analyses being done that we hope to report later this year, which are attempting to shed light on whether a patient who defers therapy even requires intensive treatment when the time for therapy does come along or not. That is something that we are hoping to learn a little bit more about. That is an area that is very interesting to me, and we hope to hear about that later in 2018.
Calzada O, Switchenko JM, Maly JJ, et al. Deferred treatment is a safe and viable option for selected patients with mantle cell lymphoma [published online ahead of print June 18, 2018]. Leuk Lymphoma. doi: 10.1080/10428194.2018.1455973.