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CLL: Experience With Chemotherapy-Free Treatment



Harry P. Erba, M.D., Ph.D.: Nathan, let’s move on to what you’ve experienced taking actually two of the most common drugs we use now in CLL [chronic lymphocytic leukemia], in your case in combination: ibrutinib, which targets BTK, the Bruton tyrosine kinase; and the other pathway, BCL2 [B-cell lymphoma 2], the protein that blocks the cells from dying, that’s where venetoclax works. You’re taking both of them. What have you experienced taking those medications? You got the drugs on a clinical trial, so cost was not an issue.

Nathan Ferguson: I started ibrutinib around January of 2017. My white cell count was about 170,000 per μL. I actually tolerated it very well initially. I had some GI [gastrointestinal] difficulty. Other than that, I tolerated it very well.

Harry P. Erba, M.D., Ph.D.: Let me ask you, what happened to your white cell count immediately after you started? Did you notice any change? Did it get better right away?

Nathan Ferguson: Mine actually went down, which I think about a third of the patients experience. I didn’t have bulky disease, so my spleen, while enlarged, wasn’t terribly enlarged, and my lymph nodes were enlarged, again, but not terribly enlarged.

Harry P. Erba, M.D., Ph.D.: So you didn’t have it go up like some patients do.

Nathan Ferguson: No. I was having the terrible hives before; I couldn’t go anywhere without bringing Benadryl with me every day. I started ibrutinib, and I think I had a mild case of the hives the second day, and by the third day the hives were gone completely, and they have not returned since. I received ibrutinib for I think three or four months, and then my white cell count went from 180,000 per μL to 40,000 per μL the next month and then down to the 20,000 per μL range. It rapidly declined, so when I started the venetoclax on month four, I was in the 14,000 to 20,000 per μL range. I started venetoclax, and I didn’t notice any real overt side effects from adding the venetoclax.

Harry P. Erba, M.D., Ph.D.: Did you just start taking it at home, the venetoclax?

Nathan Ferguson: No, I had to come in at that point. They were still working out the tumor lysis syndrome issues.

Harry P. Erba, M.D., Ph.D.: Let me stop you there. Ian, can you tell us a little bit more about that?

Ian W. Flinn, M.D., Ph.D.: Sure. Venetoclax is a fantastic drug but it has a side effect such that, in some patients, it causes sudden killing of all the lymphocytes at once. While this may sound like an attractive thing, killing leukemia, the side effect is that it can release potassium, uric acid, and other electrolytes, and there can be damage to the kidneys or arrhythmias. And so that can be a dangerous side effect. But we’ve learned how to give this drug very safely by not giving it all at once but marching up on the dose weekly until we get to the targeted dose. And through this and with careful monitoring of the blood, it can be safely given to patients, and the vast majority of patients can be treated on an outpatient basis.

Harry P. Erba, M.D., Ph.D.: Nathan?

Nathan Ferguson: I went in, I started the venetoclax. They checked my blood I believe around eight hours later, and unfortunately my disease was a little bit weirder or atypical or non-typical. Usually you’ll have problems with potassium, and actually my phosphorous went up, so I spent the night in the hospital to take care of that. And after that, I had no issues at all with the ramp up of venetoclax. I took both for eight or nine months. They rechecked everything. They did a bone marrow biopsy for MRD [minimal residual disease] negativity, and that was the Y in the trial I was in. I came back MRD-negative, so I was removed from venetoclax, and then I was either put in a placebo group or a group that continued the ibrutinib. It’s blind, so I’m not officially aware of what I’m taking now.

Harry P. Erba, M.D., Ph.D.: So you’re taking ibrutinib still?

Nathan Ferguson: Or a placebo.

Harry P. Erba, M.D., Ph.D.: Or a placebo.

Nathan Ferguson: I personally believe I’m still on it because I still have a little bit of bleeding issues, nothing horrible.

Harry P. Erba, M.D., Ph.D.: Interesting. Yes, sometimes the side effects can tell you. But let me ask you an important question. I remember this all started during your move. You felt wiped out, and a lot of times my patients who are taking even these chronic medications that target different things still feel fatigue. What happened to yours?

Nathan Ferguson: I would say my fatigue is better. However, fatigue is also a side effect of ibrutinib. I feel better than I did pre-treatment, but honestly for normal everyday life I didn’t feel horrible. It was more if I had to pick up and move something heavy, that is where it really was affecting me pre-treatment. But now I feel fine and I can work out and not feel overly tired.

Harry P. Erba, M.D., Ph.D.: Have you returned to work?

Nathan Ferguson: Yes.

Transcript Edited for Clarity

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