‘No One-Size-Fits-All’ First-Line Treatment for Mantle Cell Lymphoma

CURE, CURE® Summer 2021 Issue,

Patients can now prioritize whether durable responses to treatment or avoiding certain side effects are more valuable to them.

Progress in treating mantle cell lymphoma (MCL) has allowed patients to weigh their options for first-line therapies. Despite this progress, disease progression or recurrence is still common in these patients, so patients must be aware of their quality of life when undergoing first-line and subsequent therapies.

During a presentation at the 2021 ASCO Annual Meeting, Dr. Brian K. Link professor of internal medicine-hematology, oncology and blood and marrow transplantation at the University of Iowa in Iowa City, discussed how we can “unquestionably” do better regarding first-line therapies for MCL and why research focusing on quality-of-life outcomes is critical. CURE® spoke with Link to learn more about why frontline therapy for this disease is important even though the order in which treatment is administered may not impact outcomes as much as researchers previously believed.

Q: What is upfront therapy for MCL?

A: Mantle cell lymphoma is a serious disease. Most people, but not all, who are afflicted with mantle cell lymphoma will likely have their life shortened because of (the disease), and almost everybody will have their quality of life affected.

Invariably, for the vast majority of patients, we feel the need to alter that risk of suffering from lymphoma and/or dying from lymphoma by treating (it) with a variety of medical therapies. Surgery and radiation are not commonly part of the management plan. A high percentage of patients will have multiple courses of treatment intermittently over the course of their lifetime, and the first treatment chosen is generally what we refer to as upfront therapy.

Why may the upfront therapy patients receive be important to outcomes?

The outcomes for mantle cell lymphoma have improved substantially over the past 10 to 15 years. Two of the abstracts discussed at ASCO essentially started around 2010. Back in 2010, the prevailing evidence suggested that half of patients who were diagnosed with mantle cell lymphoma would die within the first four years. At that time, accordingly, the choice of which therapy to use first was critically important in an effort to mitigate that risk of early death.

In the subsequent 10 to 15 years, the likelihood of dying within four years has substantially reduced such that we now look at upfront treatment options for patients with mantle cell lymphoma with an eye toward what is likely going to be the second treatment and the third treatment since now more patients will be living five, 10 and 15 years. None of the treatments yet will result in (a) cure, so we still anticipate there will be multiple treatments over the course of a lifetime, and the choice of upfront treatment may not be as important as it was 10 years ago.

What are other takeaways from your presentation?

Because we now have many effective therapies, it’s important to recognize that
we as doctors do not agree on a one-size-fits-all (treatment). Thus, when patients ask “What’s the best treatment for me?” they should recognize (that) their doctor may not know of one single, best upfront therapy. They may know other patients with mantle cell lymphoma who are getting other choices for upfront therapy. They may get a second or third opinion from other doctors who may not all agree on what the best choice is for upfront therapy for them.

Patients need to recognize increasingly (that) they have a choice. Some of their choice will be philosophical. As a rule of thumb, some of the more aggressive treatments in the upfront setting may last a little longer but may involve more impact on their quality of life up front. For some patients, that may be appropriate. For other patients, they may prefer a gentler approach, recognizing that the effects may not last as long.

Because there are now so many treatments available, there is less critical importance, perhaps, on which therapy is given as first choice because the second, third and fourth treatments may have as much impact on their overall quality and duration of life as the first-line (treatment).

What is the impact to quality of life that patients may expect with these choices?

Some of the treatments require hospitalization to be administered. Others can be delivered as an outpatient basis. Some of the treatments are a little bit more intense but have a fixed duration of time, meaning three to six months of treatment and then there’s a cessation of treatment with observation. Other therapies are given chronically, often with oral medications, but sometimes intravenous medications, but the therapy goes on for a period of many years. Patients will want to assess how (they) feel about chronically being treated.

And then other things are more subtle, such as some of the treatments would cause cosmetic changes, such as hair loss, while others may result in fatigue, bowel irregularities, long-term risk of heart damage or rashes. There’s a whole variety of different side effects with the different therapies available, and patients should feel free to ask about all those options and then weigh for themselves which ones are least desirable.

During your presentation, you said MCL may be increasingly recognized as a chronic disease. What do you think this may do to the treatment of MCL or the research within this disease state?

I have fairly strong opinions about that because patients can now anticipate living a long time. Because they will have many treatment choices available to them, they’ll want to choose treatments that have an impact on something other than how long they’re going to live. We need to hear from the patients about what’s important there. Choices could include (that) they may prefer to have long periods of time where they’re not taking treatment, or it may include other elements of quality of life that we as clinical researchers and doctors can only really speculate about because we’re not the ones who are facing the decisions patients are. To the extent that patients want to have a role in shaping research moving forward, they should use patient-focused lymphoma societies such as the Lymphoma Research Foundation and advocacy groups to work with clinical researchers to develop quality-of-life outcomes in future research.

What’s an important message about MCL treatment that patients should know?

There is no one-size-fits-all in the upfront (setting), so patients will really want to be aware of that if they either seek multiple opinions from other doctors or if they seek other experiences from other patients.

(Also,) I want to emphasize that the choice of therapy that they make for first treatment is not as important as it used to be because there will undoubtedly be second treatments, third treatments and fourth treatments. We really don’t know the impact of sequence.

The last point I want to make is several of these choices would involve different short-term and long-term impacts on their quality of life and daily life. They’ll want to be aware of what their personal choices are when making these decisions and they’ll want to work with advocacy groups to build measurements of quality of life into the next generation of research trials.

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