Post-Conference Perspectives: Chronic Lymphocytic Leukemia - Episode 3

4-Year Follow-up Data From ELEVATE-TN: Frontline Acalabrutinib in CLL

Insight on the 4-year follow-up data from ELEVATE-TN and the frontline use of acalabrutinib, with or without anti-CD20 therapy, in patients with CLL.

Brad S. Kahl, MD: There was another interesting long-term follow-up presented at ASCO [American Society of Clinical Oncology Annual Meeting] this year from Dr Jeff Sharman which is a 4-year follow up of the ELEVATE Treatment-Naïve study. This was a 3-arm study that led to the approval of acalabrutinib in first-line CLL [chronic lymphocytic leukemia]. There are 3 arms in trial. Some of the patients just received single-agent acalabrutinib, but another group received acalabrutinib plus obinutuzumab the anti-CD20 monoclonal antibody. The control arm was chlorambucil and obinutuzumab with longer follow-up. 

We still see that the 2 acalabrutinib arms are performing much better than chlorambucil obinutuzumab. The interesting thing from this update has to do with the contribution of the anti-CD20 monoclonal antibody to the package. When the data was first presented and published there was a very small progression-free survival benefit for the addition of the obinutuzumab. The addition of the obinutuzumab also resulted in a few more adverse events, particularly infections. It was a trade-off: little better disease control, but little more risk for infections. With longer follow-up, the benefit of the obinutuzumab has increased slightly. For example, at 4 years, 78% of the acalabrutinib patients are still in remission vs 87% of the acalabrutinib-obinutuzumab patients, so we’re up to a 9% absolute difference in progression-free survival at 4 years. It’s starting to tip the risk-benefit ratio a little more toward the inclusion of the anti-CD20 monoclonal antibody. This can be individualized because there’s no overall survival advantage, it’s just a progression-free survival advantage.

When do I consider including the obinutuzumab? I consider it if I have younger, healthier patients, in whom I’m less worried about the infectious risks and the so-called hassle factor of getting the intravenous treatment is less of an issue. For some of our older patients, they’re frailer, so coming to clinic is a bigger inconvenience. Maybe they need transportation, or maybe they need rides. Because I’m more worried about infections in the older people, and because the back and forth of the clinic may be more problematic for them, I’m less likely to give the older patients the anti-CD20. But for the younger patients, I’d be a little more likely to include it because of this slight but significant progression-free survival advantage.

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