Updates in CLL: Strategies for Managing Toxicities and Special Patient Considerations - Episode 3

Q and A Session

Amy Goodrich, RN, MSN, CRNP, and Kirollos S. Hanna, PharmD, BCPS, BCOP, answer audience questions regarding CLL and BTK inhibitors during a question & answer session.

Amy Goodrich, RN, MSN, CRNP:Thank you for being with us, we'll take some questions. Kirollos, you can take this first question because you talked about the ALPINE study. Although the overall response rate was higher with zanubrutinib compared to ibrutinib in the ALPINE study, it's not that response rates were comparable lymphocytosis was factored in. Is that response plus lymphocytosis?

Kirollos S. Hanna, PharmD, BCPS, BCOP:This is an interesting question. The key takeaway from ALPINE is that it showed us that Zanubrutinib is effective in the relapse refractory setting CLL [chronic lymphocytic leukemia] patient. There were limitations to ALPINE, and I don't think from what we gained from it that we can say zanubrutinib is better than ibrutinib, or ibrutinib is better than zanubrutinib. You must look at the totality of evidence in terms of what we currently have. We have eight years from resonate, and it's hard to overcome that. I also mentioned the SEQUOIA trial which looked at BTK [bruton tyrosine kinase] and zanubrutinib in the frontline setting, the various cohorts, and how that was compared to chemoimmunotherapy. We combined with BCL-2. It’s exciting to see another BTK inhibitor with a favorable safety profile; zanubrutinib has a favorable safety profile. Although we see more neutropenia with zanubrutinib than ibrutinib, we see less cardiac arrhythmias and hypertension. It was exciting to see the data come out of the ALPINE study. I don't think ALPINE was a groundbreaking study, to say one drug should be utilized over the other simply based on efficacy. But yes, I do agree, there's many things you must factor in, and that's why the totality of evidence is important.

Amy Goodrich, RN, MSN, CRNP:I'll take the second question, how do you feel about zanubrutinib versus ibrutinib in frontline therapy for unmutated NOTCH117P TP53 for a 70-year-old patient? I'm not sure we have enough data to say that zanubrutinib is superior to acalabrutinib in that situation. I have been successful with a patient that I'm thinking of who is on oxygen. She's has significant cardiopulmonary disease, is in a wheelchair, and her performance status is maybe one to two days a week. She is someone who I justified getting zanubrutinib in the frontline setting because she would not survive AFib [atrial fibrillation]. Her pressure changed. I was successful in getting that to her, outlining her concomitant illnesses, the medications she was on, as well getting zanubrutinib for her. But I don't think we have enough data to say that that situation unmutated NOTCH117P and TP53 mutation warrants zanubrutinib. Hopefully it'll be approved soon, and then we can choose whichever one our gut tells us. Do you have anything to add there, Kirollos?

Kirollos S. Hanna, PharmD, BCPS, BCOP:No, I agree with you. The biggest struggle will be payer coverage, but I am optimistic that we will see an FDA approval sometime soon. I can't have a discussion today and not mention COVID-19, and your CLL population. Have you learned anything through the pandemic where you're managing your CLL patient population differently? And has it driven any prescribing habits? Are you doing more orals regarding the availability of VEN+O [venetoclax, obinutuzumab] or VEN+R [venetoclax, rituximab]? Or are you trying to get those patients on VEN+O for a year, because who knows how long the pandemic will continue, and do we just treat them for a year? I’d love to hear what you do in your practice.

Amy Goodrich, RN, MSN, CRNP:A year ago before vaccines, when we were in the throes of this, we were trying to avoid anti-CD20 monoclonal antibodies because we know that those are immunosuppressive for long periods of time, wiping out those B cells. When we knew the vaccines were coming, we knew that people who had been shortly on anti-CD20 monoclonal antibodies would not get a good immune response. We were avoiding it. The more data that has come out, especially in the CLL space showing that patients on BTK inhibitors don't get immunity. Patients who have never been treated don't get immunity. We're not as focused on that because there's not such a direct correlation between anti-CD20 and poor vaccine responses. This is a high-risk group, no matter what we're giving them. Our philosophy has changed the more that we have learned about the immune responses being shockingly negative in this patient population. How about you, Kirollos?

Kirollos S. Hanna, PharmD, BCPS, BCOP:I love hearing the different perspectives, and I can't tell you how many different perspectives I've heard. Starting off in the pandemic, the first year we were focusing heavily on keeping patients out of the infusion centers, this was pre-vaccines. That drove our oral chemo BTK prescribing for CLL, although that was predominantly what we were doing. In terms of our strategies and follow-up, that had also stayed the same. The majority of our pharmacists are following patients remotely; phone calls, televisits, those kinds of things to evaluate patients. Providers seeing patients through telemedicine, was a drastic change that we had to navigate through the pandemic. Also having an older patient population and helping them in terms of using Zoom, and how to do all these types of things. Here in 2021, at prescribing we're no longer focusing on keeping patients out of the infusion centers. In terms of vaccinations, if we can get patients vaccinated before initiating treatment with anti-CD20s, we try our best to do so by a couple of weeks.

If you look at your CLL patient population, being such an indent type of disease, you can probably, for some patients, give them three or four weeks after a vaccine series to have them mount a good immune response and then initiate treatment. If we can't do that, we still have been vaccinating. There's a lot of data in cancer care that patients don't mount that proper immune response, but we adhere to the third dose. After the initial series with Pfizer, Moderna, we do boosters for our patients if needed. We try to mount any type of immune response for our patients. One thing that I saw in 2021, there is nothing to drive anything major, but it's something we're keeping an eye on; slightly more acalabrutinib prescribing than the prior year. It's an interesting thing that we have observed in my institution. We're still doing tons of ibrutinib, but is it any new data or new evidence? Not much has come out showing one to be better than the other, other than the safety things we highlighted. That makes me think our providers may be going to a slightly better tolerated BTK inhibitor to try and minimize patient complications, patient admission, and patients that need to come in for AE [adverse events]. Those are some of the things that I've observed. It's been a struggle for all of us.

Amy Goodrich, RN, MSN, CRNP:Our next struggle related to COVID-19 will be this new two-injection. I'm blanking on the name of it that's coming out as prophylaxis for our immunocompromised patients. I'm hope we get some guidance on that because patients are asking frequently. Hopefully, we'll be able to direct the correct patients to that therapy.

Kirollos S. Hanna, PharmD, BCPS, BCOP:Absolutely, it'll be interesting. One more question is tumor lysis. One thing that we can do in this CLL patient population is BCL-2 now, right?

Amy Goodrich, RN, MSN, CRNP:Yes.

Kirollos S. Hanna, PharmD, BCPS, BCOP:What kinds of strategies are you doing? We know how to manage tumor lysis, but you get a CLL patient, and their lymphocyte count is 30,000, multiple lymph nodes greater than five centimeters. Based on uric acids slightly high, what would you do in that case? Are you always admitting these patients to initiate?

Amy Goodrich, RN, MSN, CRNP:We do not always admit patients. If their lymphocyte count is 30,000 and they don't have bulky adenopathy, we treat them in the outpatient setting. We try to reserve admittance, we're pulling them back and doing tumor lysis monitoring and hydrating them in our outpatient setting. We can get labs back relatively quickly. It's different if you're in the community where you don't have that quick turnaround for labs. That's a practice specific issue, but we look at venetoclax, that risk calculator, and we try to admit the high-risk patients and treat our low and medium risk patients in the outpatient setting.

Kirollos S. Hanna, PharmD, BCPS, BCOP:I'm with you. We've developed a good infrastructure where our infusion centers are right there connected to the hospitals. We ensure that patients can adhere to their labs and coming in with all their dose ramp-ups. It's critical in this patient population, especially during the ramp-up that you're avoiding any type of 3A, 3A4 inhibitors, because they can pose some challenges for patients. I've learned a lot from you in this hour of discussion. This was great. It was an information overload out of Ash. I want to thank our attendees and I'll turn it over to you to wrap us up.

Amy Goodrich, RN, MSN, CRNP:Thanks for those questions and for this enriching and informative discussion. I thank you Kirollos and the audience. I hope you found this engaging and helpful to enhance your understanding of management of patients with CLL, and I wish you all a great evening

This transcript has been edited for clarity.