Acalabrutinib Improves Long-Term PFS in Patients With High-Risk CLL


Danielle M. Brander, MD, discusses updated results from the ELEVATE-TN trial of acalabrutinib in patients with chronic lymphocytic leukemia.

Danielle M. Brander, MD, assistant professor of medicine at Duke University School of Medicine, discusses updated results from the ELEVATE-TN trial (NCT02475681) of acalabrutinib in patients with chronic lymphocytic leukemia (CLL).

The phase 3 trial enrolled treatment-naive patients into 3 arms who would receive acalabrutinib (Calquence) plus obinutuzumab (Gazyva), acalabrutinib alone, and chlorambucil plus obinutuzumab, respectively. Obinutuzumab was given for the first 6 months, whereas acalabrutinib was given until progression or unacceptable toxicity. The study met its primary end point of progression-free survival (PFS).

In 4-year and 5-year updated results, there were no new safety signals, with headaches and diarrhea being the most common adverse events associated with acalabrutinib, whereas neutropenia was the most common AE with obinutuzumab. The study was not powered to compare the acalabrutinib monotherapy arm with the acalabrutinib/obinutuzumab arm although a post hoc analysis showed prolonged PFS with the combination at 4 years.

Brander says that high-risk patients, including those with mutated TP53 and 17p deletions in their disease, had strong efficacy outcomes including 48-month PFS rates over 70% in each of these groups. She says this is particularly important because physicians are most concerned with the likelihood of progression when patients have these features.


0:08 | For the frontline study, the ELEVATE-TN study in longer follow-up the primary [end point] was looking at PFS and not powered to look at a difference between the arms. The longer follow-up did collect important other data. There did not seem to be new safety signals with the ongoing acalabrutinib. The most common ones seen were headaches and diarrhea for acalabrutinib, neutropenia, really only with the addition of the obinutuzumab.

0:41 | I think particularly for high-risk patients where either way the acalabrutinib was continuous, there was promising still long-term follow-up data about the PFS at 4 to 5 years out being over 70% for those patients with [deletion] 17p or [mutated] TP53, which again, any of these BTK [Bruton tyrosine kinase] inhibitors or novel agent studies showing these long PFS for the highest-risk patients is, I think, particularly important because those are the patients we become most concerned about with novel agents of risk of progression.

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