ONCAlert | Upfront Therapy for mRCC

Managing BCL2 Inhibitor AEs in Chronic Lymphocytic Leukemia

Targeted Oncology
Published Online:12:00 PM, Tue August 6, 2019

Harry Erba, MD, PhD: Let’s talk about toxicity with BCL2 inhibition and venetoclax. Let’s start with tumor lysis syndrome [TLS]. I know you live and breathe this, and you do it every day, but for the people listening to us, how do you risk stratify for TLS, and how do you approach that management with venetoclax?

Javier Pinilla-Ibarz, MD, PhD: Theoretically, we used to say that we deal with TLS in any condition that we do. We use prophylaxis with allopurinol, in some cases with rasburicase and definitely with hydration. Specifically with venetoclax, its very nice tables in the prescription information will tell you how you define high, intermediate, and low. And it’s pretty much based on lymphocyte counts and size of the lymph nodes. More than 25,000 and more than 5 to 10 cm of lymph node will define a very high risk. This combination—or less combination of that and the absence of these 2 features—will define low risk.

This was done in the early trials of venetoclax to really try to see who the patients were who were worth having very close monitoring. In real life, this may be different because obviously with the debulking agent that we have, most of the patients behave as intermediate or low risk, and those patients can easily be managed in the outpatient setting. However, obviously, we need to really be aware of the recommendation of the FDA and the prescription information on how to follow them before and after. You have to really make sure the patients are safe.

Very interestingly, we have done the same thing with obinutuzumab, and we know that if we look, we’re going to find it. Again, I think it’s important to be cautious. I don’t think we should really be too afraid about this TLS, because I think it’s something we have been dealing with. It’s not really, really high in terms of rate of events, and it’s something that’s easily managed if you do things properly.

Harry Erba, MD, PhD: One of the things I actually just learned recently, because I don’t take care of patients with CLL [chronic lymphocytic leukemia] much anymore, is that it’s advised that patients who are going to be treated as an outpatient actually take their drug at 6 AM, even before they get to the clinic for monitoring.

Javier Pinilla-Ibarz, MD, PhD: Sure, sure.

Harry Erba, MD, PhD: Do you do that?

Javier Pinilla-Ibarz, MD, PhD: Typically, we meet with the patient in the morning, we do an early lab, 7 AM. If the labs are fine, we let them take the drug, and then we see them at the end of the day.

Harry Erba, MD, PhD: You keep them there in the clinic.

Javier Pinilla-Ibarz, MD, PhD: They go—they can really go anywhere—and they come back. They see the labs, so we send them home. Again, I think it’s something that we follow, but I have to tell you we don’t have any problems. We just follow the recommendation of the prescription information.

Harry Erba, MD, PhD: As you know, we are now using venetoclax in AML [acute myeloid leukemia] patients. And 1 of the issues I think we need to deal with is neutropenia. Is that much of an issue here in CLL?

Javier Pinilla-Ibarz, MD, PhD: Absolutely. Neutropenia is 1 of the issues that has also been seen in the trial that was presented at the American Society of Clinical Oncology Annual Meeting, the CLL14. And the reason is because we now know you do see some neutropenia. We have to be careful because in the ramp-up period, even with the venetoclax going to 400 mg, the additional use of a monoclonal antibody that classically produce neutropenia can really produce high levels of neutropenia. So we have to be careful. We do dose modification, the same thing that I’m sure you do, Harry, in AML. As you know, my colleagues and I deal with same problems, and sometimes we need to lower the dose and we need to continue.

Harry Erba, MD, PhD: How about nonhematologic toxicity? Any specific things that you see?

Javier Pinilla-Ibarz, MD, PhD: I have to admit that this drug is extremely well tolerated, but sometimes there are some GI [gastrointestinal] upsets, nausea, maybe mild diarrhea. In general, all of us who have experience with this drug are very surprised that—besides the hematologic toxicity that you’re referring to with the neutropenia that have to be taken into consideration—it is well tolerated. Patients do extremely well, even patients with multiple comorbidities and older age. However, another thing that’s important to keep in mind is the interaction, something we are dealing all the time with cardiac medications, with antibiotics. As you know, in AML, it’s a very big thing when you really need to add voriconazole or anything else. So it’s something that we need to keep in mind and always really aim to adjust the dose.

Harry Erba, MD, PhD: In terms of supportive care, what do you recommend in terms of vaccinations?

Javier Pinilla-Ibarz, MD, PhD: As you know, on these drugs, we do not recommend vaccination. Maybe the reason is the vaccination won’t work. Really, we’re targeting the cells, we’re really going to produce the antibodies. This is the reason we do not recommend vaccination to these types of patients who are taking these drugs.

Harry Erba, MD, PhD: I have to assume there must be some kind of contraindication for women of child-bearing potential, lactation.

Javier Pinilla-Ibarz, MD, PhD: Absolutely. This is the standard, classical approach for any kind of targeted drugs that we are using.

Harry Erba, MD, PhD: What do you do at Moffitt Cancer Center to prepare patients for the potential adverse events with venetoclax? Any specific education methods?

Javier Pinilla-Ibarz, MD, PhD: Absolutely. As with any drug, as we do with ibrutinib or we do with venetoclax, we really have a very long conversation about the potential things. Some people can be scared sometimes: “Oh, doctor, why are you telling me these things?” I think it’s best to be educated and prepared. And it’s very likely we will discuss that, most likely, they won’t have that. But they need to be ready because we want to hear about the adverse effects really happening, so we can really take care immediately and continue therapy.

Transcript edited for clarity.

Harry Erba, MD, PhD: Let’s talk about toxicity with BCL2 inhibition and venetoclax. Let’s start with tumor lysis syndrome [TLS]. I know you live and breathe this, and you do it every day, but for the people listening to us, how do you risk stratify for TLS, and how do you approach that management with venetoclax?

Javier Pinilla-Ibarz, MD, PhD: Theoretically, we used to say that we deal with TLS in any condition that we do. We use prophylaxis with allopurinol, in some cases with rasburicase and definitely with hydration. Specifically with venetoclax, its very nice tables in the prescription information will tell you how you define high, intermediate, and low. And it’s pretty much based on lymphocyte counts and size of the lymph nodes. More than 25,000 and more than 5 to 10 cm of lymph node will define a very high risk. This combination—or less combination of that and the absence of these 2 features—will define low risk.

This was done in the early trials of venetoclax to really try to see who the patients were who were worth having very close monitoring. In real life, this may be different because obviously with the debulking agent that we have, most of the patients behave as intermediate or low risk, and those patients can easily be managed in the outpatient setting. However, obviously, we need to really be aware of the recommendation of the FDA and the prescription information on how to follow them before and after. You have to really make sure the patients are safe.

Very interestingly, we have done the same thing with obinutuzumab, and we know that if we look, we’re going to find it. Again, I think it’s important to be cautious. I don’t think we should really be too afraid about this TLS, because I think it’s something we have been dealing with. It’s not really, really high in terms of rate of events, and it’s something that’s easily managed if you do things properly.

Harry Erba, MD, PhD: One of the things I actually just learned recently, because I don’t take care of patients with CLL [chronic lymphocytic leukemia] much anymore, is that it’s advised that patients who are going to be treated as an outpatient actually take their drug at 6 AM, even before they get to the clinic for monitoring.

Javier Pinilla-Ibarz, MD, PhD: Sure, sure.

Harry Erba, MD, PhD: Do you do that?

Javier Pinilla-Ibarz, MD, PhD: Typically, we meet with the patient in the morning, we do an early lab, 7 AM. If the labs are fine, we let them take the drug, and then we see them at the end of the day.

Harry Erba, MD, PhD: You keep them there in the clinic.

Javier Pinilla-Ibarz, MD, PhD: They go—they can really go anywhere—and they come back. They see the labs, so we send them home. Again, I think it’s something that we follow, but I have to tell you we don’t have any problems. We just follow the recommendation of the prescription information.

Harry Erba, MD, PhD: As you know, we are now using venetoclax in AML [acute myeloid leukemia] patients. And 1 of the issues I think we need to deal with is neutropenia. Is that much of an issue here in CLL?

Javier Pinilla-Ibarz, MD, PhD: Absolutely. Neutropenia is 1 of the issues that has also been seen in the trial that was presented at the American Society of Clinical Oncology Annual Meeting, the CLL14. And the reason is because we now know you do see some neutropenia. We have to be careful because in the ramp-up period, even with the venetoclax going to 400 mg, the additional use of a monoclonal antibody that classically produce neutropenia can really produce high levels of neutropenia. So we have to be careful. We do dose modification, the same thing that I’m sure you do, Harry, in AML. As you know, my colleagues and I deal with same problems, and sometimes we need to lower the dose and we need to continue.

Harry Erba, MD, PhD: How about nonhematologic toxicity? Any specific things that you see?

Javier Pinilla-Ibarz, MD, PhD: I have to admit that this drug is extremely well tolerated, but sometimes there are some GI [gastrointestinal] upsets, nausea, maybe mild diarrhea. In general, all of us who have experience with this drug are very surprised that—besides the hematologic toxicity that you’re referring to with the neutropenia that have to be taken into consideration—it is well tolerated. Patients do extremely well, even patients with multiple comorbidities and older age. However, another thing that’s important to keep in mind is the interaction, something we are dealing all the time with cardiac medications, with antibiotics. As you know, in AML, it’s a very big thing when you really need to add voriconazole or anything else. So it’s something that we need to keep in mind and always really aim to adjust the dose.

Harry Erba, MD, PhD: In terms of supportive care, what do you recommend in terms of vaccinations?

Javier Pinilla-Ibarz, MD, PhD: As you know, on these drugs, we do not recommend vaccination. Maybe the reason is the vaccination won’t work. Really, we’re targeting the cells, we’re really going to produce the antibodies. This is the reason we do not recommend vaccination to these types of patients who are taking these drugs.

Harry Erba, MD, PhD: I have to assume there must be some kind of contraindication for women of child-bearing potential, lactation.

Javier Pinilla-Ibarz, MD, PhD: Absolutely. This is the standard, classical approach for any kind of targeted drugs that we are using.

Harry Erba, MD, PhD: What do you do at Moffitt Cancer Center to prepare patients for the potential adverse events with venetoclax? Any specific education methods?

Javier Pinilla-Ibarz, MD, PhD: Absolutely. As with any drug, as we do with ibrutinib or we do with venetoclax, we really have a very long conversation about the potential things. Some people can be scared sometimes: “Oh, doctor, why are you telling me these things?” I think it’s best to be educated and prepared. And it’s very likely we will discuss that, most likely, they won’t have that. But they need to be ready because we want to hear about the adverse effects really happening, so we can really take care immediately and continue therapy.

Transcript edited for clarity.
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