ELEVATE-RR: Safety Data

EP: 1.Introduction and CLL Background

EP: 2.ELEVATE-RR Study Overview

EP: 3.Patient Characteristics in ELEVATE-RR

EP: 4.ELEVATE-RR: Efficacy Data

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EP: 5.ELEVATE-RR: Safety Data

EP: 6.Key Takeaways and Clinical Implications

EP: 7.Unmet Needs and Future Directions in CLL

EP: 8.Recap: Noninferiority Comparison of Acalabrutinib and Ibrutinib for Previously Treated CLL

Michael R. Bishop, MD: The next thing we want to turn to is where Bruce beautifully led into the discussion of this article. If they’re equally efficacious, the next thing you want to do is look at the adverse effect [AE] profile. You can see on this slide that the incidence of diarrhea, one of the most common adverse effects associated with Bruton tyrosine kinase [BTK] inhibitors, is 35% diarrhea vs 46% with ibrutinib. Grade 3 was approximately 5% with ibrutinib vs 1.1%. There was a higher incidence of headache associated with acalabrutinib, about 35% vs 20% with ibrutinib. Grade 3 was a little less than 2% grade 3 with acalabrutinib, but 0 with ibrutinib. Cough was 28.9% vs 21.3%, with low incidence of grade 3.

One of the most important things with treatment with any regimen for chronic lymphocytic leukemia is infection. I always emphasize to my patients that because they’re immune-compromised, from the beginning they have to be observant for any form of infection with a BTK inhibitor. Upper respiratory infection [URI] was 27% vs 25% with ibrutinib. The incidence of grade 3 is approximately the same between the 2 agents. Anemia, which Bruce brought up, is a common finding, at 22% vs 19%. I was mildly surprised about neutropenia. It’s a little lower: 21% vs 24%. The overwhelming majority of the time, these are going to be grade 3, 20% with acalabrutinib vs 23% with ibrutinib. It’s important to continue to monitor patients. Fatigue was common. Arthralgias are an underappreciated adverse effect that we can see with this, 16% with acalabrutinib and 23% with ibrutinib, which was slightly statistically higher than acalabrutinib.

The median durations of treatment for these 2 drugs were 38 months and 35½ months, respectively. Patients generally stay on the drug for a significant amount of time, which is reflective of the progression-free survival curves that we previously saw. Adverse events led to treatment discontinuation in approximately 15% of patients on acalabrutinib and 21% on ibrutinib. Treatment-emergent AEs that caused death were seen in 6% of patients with acalabrutinib vs 9.5% with ibrutinib.

Bruce, are these the adverse events that you’re seeing in your patient population?

Bruce B. Bank, MD: Yes, although I haven’t been sensitive to arthralgias as an adverse effect. My experience is that a lot of patients complain of arthralgias. I tend to think it has something to do with being older and having degenerative disease. Maybe it’s these drugs. But that’s about right. I haven’t seen a lot of URIs in my patients. I don’t know why that is.

Michael R. Bishop, MD: It’s interesting. In this patient, when they were looking at it, I was struck because I still call it PCP [pneumocystis pneumonia]. Maybe that’s me being old school. But there was quite an incidence, and it’s another thing that’s important. I saw a lot of aspergillus on a relative scale among the patients. I wouldn’t have thought about that. I have all my patients on Bactrim if I can to prevent that. I don’t know how it is with you. I guess it’s dependent on the neutropenia. I’m not typically putting them on an azole with aspergillus coverage. I put a lot of my patients on fluconazole. What’s your clinical practice like?

Bruce B. Bank, MD: I grew up when prophylactic antimicrobials were frowned upon in general and seen as a mechanism for developing drug-resistant microorganisms. I’ve also been married for many years to an infectious disease specialist. Having said that, I’ve seen the light the last few years that maybe these patients deserve prophylaxis. I tend to put them on antibacterial stuff, usually Bactrim if they’re not allergic, and an azole to minimize the risk of those nasty infections that they can get.

Michael R. Bishop, MD: The important thing we always say is that they have to be on an antiviral as well.

Bruce B. Bank, MD: Yes.

Michael R. Bishop, MD: Let’s come back to what we think about with a Bruton tyrosine kinase inhibitor: the cardiac events, particularly atrial fibrillation and atrial flutter. When we look at hypertension, the incidence of any grade is significantly different. It’s 23% with ibrutinib vs 9.5% with acalabrutinib. When you look at grade 3 hypertension, it’s 4% vs 9.1%. It’s highly significant for any grade, and it reaches statistical significance when we get to grade 3.

When we look at overall cardiac events, it’s relatively similar: 24% vs 30% with acalabrutinib vs ibrutinib. When we look at grade 3 events, it’s very similar again: 8.6% vs 9.5%. Neither of those reached statistical significance. When we come to atrial fibrillation or flutter, it’s 9.4% with acalabrutinib and 16% with ibrutinib, which was statistically significant at 0.02. Grade 3 was very similar, 4.9% vs 3.8%, which wasn’t statistically significant. Remembering that the median treatment for both of these was 38 vs 35½ months, it didn’t necessarily appear to get worse over time. No atrial fibrillation events led to discontinuation of acalabrutinib vs 2.7% with ibrutinib. Those are all the major points that we wanted to make.

Transcript edited for clarity.