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Expert Breaks Down the Three Treatment Modalities Currently Being Investigated in CLL


“There’s a lot of work to do in CLL,” said Dr. Mazyar Shadman about the treatments currently being investigated in CLL. “We have been very fortunate to be able to provide a lot of options to our patients, but we shouldn't forget that there's a long way to go.”

In a recent interview with CURE®, Dr. Mazyar Shadman of the Seattle Cancer Care Alliance walked through the three types of treatment modalities being examined in chronic lymphocytic leukemia (CLL) right now: combination therapies that offer the best choice in the first line setting, targeted therapies or immunotherapy approaches that offer a wider range of options, and finally, safer drugs that offer less side effects or toxicities than other treatments.

“There’s a lot of work to do in CLL. We have been very fortunate to be able to provide a lot of options to our patients, but we shouldn't forget that there's a long way to go,” said Shadman.


The goal is to come up with a time-limited treatment that's not chemotherapy, so you can give a non-chemotherapy treatment to patients and then stop and then have a remission for years, and hopefully cure the patient. That's the goal for first line. What are we doing to achieve that? There are a number of clinical trials that are combining all these novel agents together, so combination studies, whether it could be ibrutinib in combination with venetoclax and obinutuzimab. It could be ibrutinib and venetoclax.

Studies have looked at acalabrutinib and venetoclax. And so, in principle, we are trying to use our best drugs up front, going for the disease as strong as we can, with a goal of getting rid of every cell of cancer in the body and then stopping, and then cure the patient or giving them years of remission. So, a lot of the studies that are happening right now are using combination therapies. That's the forefront and probably the biggest thing.

The second category of studies that are happening in the CLL world are to find even better drugs. We have great drugs, but there are still patients whose disease may become refractory or they can relapse after being treated with this great drug. So, there are a couple of new categories that are being tested as a new CLL drug. That could be immunotherapy-based therapies or novel drugs, those are in development. We have a next generation BTK inhibitor category and those are the drugs that inhibit the BTK enzyme but with a different mechanism so you can potentially use them in patients who didn't respond to ibrutinib or acalabrutinib or drugs like that. That category is growing now, and we have studies that are looking at those drugs. We have new targets, I mean, I don't want to name all the drugs, and then bispecific antibodies, which is a form of immunotherapy, and then more, of course, CAR T-cell therapy. So these are just more effective treatments, and this is our second category.

The third category would be drugs that are just safer. They are maybe not better than the current drugs, but this is fewer side effects or with a better toxicity profile. And there's a long list of drugs that are in that category.

So, in general, combination therapies. Number two would be better targeted therapies or immunotherapy approaches, and number three would be safer drugs.

There’s a lot of work to do in CLL. We have been very fortunate to be able to provide a lot of options to our patients, but we shouldn't forget that there's a long way to go. These drugs come with side effects, and they are not 100% effective, so, we need to work on both the efficacy and safety of these products. A lot of these treatments are still given forever, so you have to work on that. And we want to make sure that our patients are both disease-free, but not on a medication. So clinical trials are critical.

And I think CLL, or in general in oncology, the patient will benefit from, if not being followed by, at least being in close contact with a person or with a center that's focused on their disease, so they know what's happening in the field and whether they're missing trials or new trials that are going on, and (who) they can ask about their options.

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