'Watch and Wait' Versus Therapy Initiation in Follicular Lymphoma

Insights From:Bruce D. Cheson, MD, FACP, FAAAS, Georgetown University Hospital; Shuo Ma, MD, PhD, Northwestern University Feinberg School of Medicine; Richard R. Furman, MD, Weill Cornell Medical College


Shuo Ma, MD, PhD:
The timing of treatment for follicular lymphoma partly depends on the staging of the disease. For a patient who has limited stage follicular lymphoma, the treatment purpose is curative, because many of those patients when treated with radiation therapy can achieve a cure. For those patients, as soon as we make a diagnosis, we tend to treat them.

Actually, the majority of the follicular lymphoma patients were diagnosed with advanced stage. So, for those patients, who are not symptomatic, we tend to choose the "watch and wait" approach. The time to consider treatment is when patients are having either symptomatic disease, such as the B symptoms with fevers, chills, night sweats, weight loss due to poor appetite, or severe fatigue. So those B symptoms are an indication for treatment. In addition, if a patient is having bulky lymphadenopathy that's causing symptoms or causing impending organ compression, that's another indication.

And also for patients who are having organ damage, such as renal failure due to compression or due to pleural effusions, or ascites from the lymphoma compressing on the lymphatic system,that's another consideration of treatment. And also for patients who are developing cytopenia due to the lymphoma burden in the bone marrow. When the bone marrow is not functioning well, due to the overwhelming amount of lymphoma cells in the marrow, that's another indication to treat. For the patients who are having no symptoms and no bulky adenopathy and no organ compromise, those patients can be just a "watch and wait" with periodic monitoring.

Bruce D. Cheson, MD: It seems sort of antithetical, but “watch and wait” has been a standard of care for patients with follicular lymphoma. The patients come in and you tell them they've got cancer, "I'm not going to treat you, come back in three months," and it's very hard for them to accept that. But it's based on a number of clinical trials—most of them quite old—in which patients with low tumor burden disease who are asymptomatic are randomized to early intervention or not. And the outcome was the same. So “watch and wait” has become a standard because, why subject patients to chemotherapy if it's not going to be beneficial and if they can wait and get treated later? And as I tell patients, every treatment we give them has toxicity, expense, and nuisance. And if you wait long enough, newer drugs will come along that are more effective and less toxic, and that's where we are now.

We have a plethora of new drugs out there, such as idelalisib and others, which target pathways within the B-cell. Many of these new drugs are oral, they're very effective, and they're well-tolerated. Has this impacted when we start treatment of patients? In my mind, no. I have patients with follicular lymphoma I have been watching and waiting for 10 or 15 years. They've never been treated. Why should I give them any form of therapy?

So “watch and wait” is still a very standard approach until there are specific indications to treat the patient, such as disease-related symptoms, progressive or bulky lymphadenopathy, progressive splenomegaly, and other features such as that. If a patient has that, then we discuss the various treatment options. But in the absence of evidence of progressive disease or bulky disease, or disease-related symptoms, watching and waiting remains a very viable option for patients with follicular lymphoma.

Richard R. Furman, MD: With follicular lymphoma patients, the goal is always going to be to improve progression-free survival, and ultimately, hopefully that will translate into improvement in overall survival. The important consideration, whenever you're discussing overall survival, is to make sure that our therapy isn't going to diminish that outcome. So, it certainly is important to sequence the more benign therapies versus the more aggressive therapies in a way that's going to allow the toxicities to be delayed as long as possible.

One of the most important pieces of data, that we will eventually get, is whether or not bendamustine is associated with long-term secondary myeloid neoplasia and needs to be avoided in these patients. We already know from the current data that bendamustine, plus Rituxan, is actually better and less toxic than R-CHOP, and that certainly has had a tremendous impact upon how we care for our patients. But with the advent of other therapies, like lenalidomide and Rituxan, or idelalisib, Ibrutinib, and other B-cell receptor antagonists coming down, as well as other small molecule inhibitors, the hope would be that we could even push out the more toxic chemotherapy agents further.
Transcript Edited for Clarity
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