Simon Rule, MD, PhD
For young, fit patients with mantle cell lymphoma (MCL), the best frontline treatment approach could be observation, according to Simon Rule, MD, PhD.
Rule, a professor of hematology at Plymouth University Medical School in the United Kingdom, acknowledged that BTK inhibitors have positively changed the landscape in the relapsed/refractory setting. However, he stressed that these novel approaches are potent, and physicians should save these types of therapies for more aggressive stage disease.
In patients who present with low-volume, asymptomatic MCL, Rule noted, the “watch and wait approach” is appropriate because there is no benefit to treating them early in their disease.
There is an ongoing trial in the United Kingdom testing the efficacy of this strategy. In the study, newly diagnosed patients with MCL go into a biobank and researchers follow the course of their disease. Of the patients who were clinically eligible to be watched and waited on, over 30% did not progress after 1 year. Rule says this is important because hematologists won’t know if a patient’s disease is indolent if they are immediately treated.
In patients who do require active treatment, agents such as bortezomib (Velcade) and lenalidomide (Revlimid) have been studied as first-line therapy for patients with MCL. Some of the most highly anticipated data, though, are with the BTK inhibitors ibrutinib (Imbruvica) and acalabrutinib (Calquence).
Additionally, the SHINE study (NCT01776840) is a two-arm phase III trial of ibrutinib in combination with bendamustine plus rituximab (BR) in patients with newly diagnosed MCL. The first arm is placebo, given orally once daily plus 90 mg/m2
of bendamustine intravenously (IV) on days 1 to 2 of cycles 1 to 6, plus rituximab at a dose of 375 mg/m2
IV on day 1 of cycles 1 to 6. If complete or partial response (PR) is achieved, 375 mg/m2
of rituximab is given on day 1 of every second cycle for a maximum of 12 cycles. The second arm contains 560 mg of oral ibrutinib once daily plus the same BR dosing regimen.
In an interview with OncLive,
Rule discussed the observational and active therapeutic approaches for patients with MCL.
OncLive: What is the current management for patients with MCL?
For younger patients, it is pretty well established that it is a high-dose cytarabine-based regimen. It is usually followed by a stem cell transplant, followed by rituximab maintenance. That is pretty much the standard. There are a number of different ways you can give high-dose cytarabine.
What regimens are in development?
Of course, the drugs that have made the biggest impact in this disease are the BTK inhibitors. The question is if we need these drugs for the frontline treatment of younger patients. These patients are off drugs and living a normal quality of life. When they relapse—because everyone relapses—that is when we introduce these novel therapies.
There are a number of ongoing studies in the United Kingdom that are going to challenge the traditional paradigm. Specifically, do we need transplant? That is something for the future. It is difficult in the younger patients to use anything other than the traditional chemotherapy. When I give presentations about this disease, I always say, "Don't forget that chemotherapy works." There is a lot of excitement about new drugs, obviously. However, the odd thing about these drugs is that they will probably be more valuable for the older, frailer patients. Be cautious about using new drugs early.
Please explain the watch and wait approach.
I have been watching and waiting MCL for a long time—over a decade. People thought I was mad when I first started doing it, and now it is becoming pretty well established. Watching and waiting does not disadvantage patients. If they are asymptomatic with low-volume disease, there is no benefit in treating someone early in treatment if they are in good health. It sounds counterintuitive with an aggressive cancer, but the answer is that when you treat this disease, it inevitably relapses. When it relapses, it is a much more difficult disease to treat. You won't know if someone has indolent disease unless you leave them alone.