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Beyond CLL: Richter’s Transformation and Secondary Cancers

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Published on November 20, 2020

Understanding Risk for Secondary Cancers and Richter’s Transformation in CLL

Are chronic lymphocytic leukemia (CLL) patients at risk for secondary cancers? What preventative measures should they take? What is a Richter’s transformation, and why does it occur? What questions should patients ask their doctors to track the progress of their CLL?

Listen in as two CLL specialists, Dr. Paolo Caimi, Hematologist/Oncologist at University Hospital (UH) Cleveland Medical Center, and Dr. Brian Hill, Director of the Lymphoid Malignancies Program and the Cleveland Clinic Taussig Cancer Institute, answer these questions and share their expert knowledge.

This program is sponsored by AbbVie, Inc. and Genentech, Inc. These organizations have no editorial control. It is produced by Patient Power, and Patient Power is solely responsible for program content.

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Transcript | Beyond CLL: Richter’s Transformation and Secondary Cancers

Are CLL Patients at Risk for Secondary Cancers?

Dr. Caimi: The cancers that we see in people with CLL can occur from two different reasons, right? One of them is for people primarily, who have been treated with chemotherapy, can have secondary cancers or secondary bone marrow problems like what you have. But on the other hand, people with CLL have a slightly increased risk of other cancers because their immune system is actually good at trying to detect cancers and trying to remove very low levels of cancer cells in our body. And one of the things that we know is that people with CLL, have a slightly increased risk of other cancers just from having CLL.

That's why one of the things that we recommend to our patients where something is very common, is actually to have skin cancers. So, I tell my patients to be careful with their sun exposure, but also to see a dermatologist often, and usually at least once a year.

Chemotherapy, in the old style of chemotherapy that we used to use has a higher risk of secondary cancers than the current ones. I’d say the new drugs like ibrutinib (Imbruvica), venetoclax (Venclexta), the antibodies, have much lower risk, if any. But we also need to use them for a longer period of time to tell you, hey, 30 years down the line there’s something else that’s happening. And I think that’s something we need to learn a little bit more.

Dr. Hill: I think it’s important to just remember that the way fludarabine (Fludara) and bendamustine (Bendeka), these things work is by damaging the DNA. That’s actually their known mechanism of action is they damage the DNA in the cancer cell which leads to the cell dying. The targeted inhibitors really don’t cause DNA damage. I wouldn’t expect to see an increased risk of secondary cancers with these agents, but any drug needs to be monitored for, really decades to see if there’s any signal that’s unexpected.

I think skin cancer is the big one, and then sort of immuno-deficiency is the other, so a common question we get is, is my immune system abnormal? And by definition, because you have CLL, even if you're on watch and wait, I always tell people, it may be an A minus, it's not a perfect immune system, but, what's more important is how frequently they're getting infections. If they're not winding up in the hospital with pneumonia or serious infections, usually people's immune system keeps them pretty safe. So outside of skin cancer and maybe some increased risk of infections like shingles, other organ systems are not really affected in a major way.

What is Richter’s Transformation?

Dr. Caimi: When you first get diagnosed with CLL, your doctor tells you well this is going to be a really long road, it's going to be slowly progressive, and you may need treatment within a period of time.

When Richter’s transformation occurs, the cells change to a much more aggressive type of lymphoma, and it doesn't always happen all over, may just be in one spot where one lymph node or a couple of places, but they're growing much faster. And usually, they behave in a way of the lymphomas that, when we meet you, we discuss starting chemotherapy. The additional problem is because there's an underlying CLL that changes to happen in the cells, and usually enough that they're going to make these Richter cells more resistant to treatment.

And the additional problem is that, because it's not a common scenario, we don't necessarily know as well as we do for other lymphomas, how to treat it. We treat it with the same chemotherapy, but it doesn't work always that well. We have newer drugs, we have newer combinations that we're looking at, but it's a somewhat more serious situation where we need to bring it down relatively quickly.

If you're less young, you may have more trouble tolerating the much more intensive treatment. And now we're going to what we said, old chemotherapy, the chemo that usually makes you lose your hair. And now we're looking at whether we can combine it with the drugs that are used in CLL, so that we can have an additional boost to that. It is not common. I'd say, probably the general perception is probably less than 1% per year of CLL or around there.

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