Dr Jallouk Discusses Advancements In Lymphoma

In recognition of September as Blood Cancer Awareness Month, Andrew Jallouk, MD, PhD, assistant professor of medicine at Vanderbilt University Medical Center, discusses the past and future of lymphoma treatment in an interview with Targeted Oncology.

Over the past decade, there has been a significant increase in the number of approved drugs for treating lymphoma. Before the mid-2010s, the primary treatments were chemotherapy and rituximab (Rituxan), which, while great advancements, often left patients with limited options if they relapsed.

Now, new therapies have emerged, including targeted antibodies, bispecific antibodies, Bruton tyrosine kinase (BTK) inhibitors, and chimeric antigen receptor (CAR) T-cell therapies. These advancements have led to treatments for some diseases that previously lacked them, and in certain cases, have provided cures for conditions that were once incurable.

Targeted Oncology: What do you consider to be the biggest challenges today when treating lymphomas?

In the past few in the past decade or so, we've had a huge number of drugs approved for treatment of lymphoma. They tend to work well, but a lot of them, for example, CAR T-cell therapies and bispecific antibodies, require quite a bit of infrastructure to give safely. So, one of the biggest barriers we've seen is really access to these therapies, especially for people who may live in a more rural setting or don't really have good access to oncologic care.

Secondly, while many of these treatments do work well, there is still a subset of diseases, especially rare or high-risk lymphoma subtypes, that don't respond. So, developing treatments that work for those conditions is another major obstacle.

Finally, what would we refer to as personalized medicine—making sure we give the right treatment to the right patient in the right amount. Trying to optimize that has been a major area that we've been trying to advance, and there are some new technologies that are helping to support that now

What have been the biggest advancements in treating lymphoma in recent history?

If we look at the past decade, there have been a huge number of approvals. Before the mid-2010s, really, the main treatments for lymphomas were basically chemotherapy and then rituximab, which was a great advance. But for a long period, that's pretty much all we had. That did cure a subset of lymphomas, but usually, if [a patient] relapsed after that, the chances of cure went way down.

Now, we have targeted antibodies that deliver the chemo very specifically to certain cell types. We have bispecific antibodies. We've got targeted therapies like BTK inhibitors. We've got CAR T-cell therapies. All of these have come about just in the past 10 years or so. So, for some diseases that didn't have good treatments, we now have great treatments that can provide patients with high quality of life for a long period. In some cases, we have treatments that can cure conditions that otherwise would not have been cured.

I think the breadth of all the different therapies that are available now has been a huge advance in the lymphoma field, and we're still trying to figure out the best way to use all of them.

How have treatment paradigms shifted for indolent and aggressive lymphomas?

Aggressive lymphomas can grow quickly, and so we treat them [as such]. With those, we say that there is a potential chance for cure. Indolent lymphomas grow more slowly. The historical paradigm has been, since they grow slowly, we treat them, they shrink a little bit, and then we wait for them to come back and then treat again.

I think, depending on the type of lymphoma, what patients are looking for differs a little bit. For the aggressive lymphomas, we highlight curative potential. Like I said, we now have different treatments that could potentially cure these aggressive lymphomas, even after they've come back after a previous treatment.

In the indolent lymphoma space, I think what we focus on is quality of life and time off treatment. Patients very much value not having to come into their doctor's office to get a treatment every week or every month or not having to take a pill that gives them [adverse] effects. So, finding fixed-duration or one-time treatments that can give a good response years without having to have the [adverse] effects of continuous treatment has been huge. Now, there is even a potential with some of the newer therapies that we may be curing some of these potentially incurable subtypes. I think those aspects of treatment are important for patient quality of life.

What research is on the horizon that you’re most excited about?

The first has to do with personalized medicine: making sure we're giving the patients the right amount of treatment that they need. Measurable residual disease, or MRD, testing is used for a variety of other cancers but has not really gotten into the lymphoma treatment paradigm until recently. The idea here would be, in the curative-intent setting, for example, trying to find out when the cancer is completely gone and when we can stop treatment. I think that's going to be an exciting technology and one that will really change the way we handle lymphoma treatment.

Then, a lot of what I do are cellular therapies like CAR T-cell therapies, and for these, access has really been an issue. There have been a lot of advances in the immunotherapy space to try to improve access. There are a lot of exciting things coming down the pike in term of so-called in vivo CAR T. Anything that can improve patient access to these therapies is really what we're looking for.