Susan M. O’Brien, MD, discusses the long-term results of the ELEVATE TN trial in patients with previously untreated chronic lymphocytic leukemia.
Susan M. O’Brien, MD, associate director for clinical science at the Chao Family Comprehensive Cancer Center, medical director of the Sue & Ralph Stern Center for Clinical Trials & Research, and professor at the UC Irvine School of Medicine, discusses the long-term results of the ELEVATE TN trial (NCT02475681) in patients with previously untreated chronic lymphocytic leukemia (CLL).
The randomized phase 3 trial consisted of 3 arms: acalabrutinib (Calquence) plus obinutuzumab (Gazyva), acalabrutinib alone, and chlorambucil plus obinutuzumab. The anti-CD20 antibody obinutuzumab was given for the first 6 months, whereas acalabrutinib was given until progression or unacceptable toxicity.
Initially, both acalabrutinib arms showed better progression-free survival (PFS) compared with chlorambucil plus obinutuzumab. However, at a 5-year update, the acalabrutinib plus obinutuzumab arm had a superior 60-month PFS rate of 84%, whereas the acalabrutinib alone arm was 72% and the control arm was 21%.
O’Brien says that during the COVID-19 pandemic, there has not been as much use of obinutuzumab because of the increased risk of infection. As COVID-19 becomes less of a concern, using the combination in patients with CLL would be supported based on this PFS. However, she notes that patients with p53 mutations and deletion 17p did not appear to do better with the combination than acalabrutinib monotherapy.
0:08 | The ELEVATE TN trial was the trial that led to the frontline approval of acalabrutinib either alone or with obinutuzumab, and it's up to the physician to choose. And that was a 3-arm trial of acalabrutinib single-agent or acalabrutinib given with obinutuzumab. In that combo, the obinutuzumab was front loaded and stopped after 6 months, and in both acalabrutinib arms, acalabrutinib was continued indefinitely until the patient progressed or they have toxicity that necessitated stopping. The control arm in that trial was chlorambucil and obinutuzumab. And that trial showed that either acalabrutinib arm produced significantly better PFS than the chlorambucil-based therapy.
0:51 | Interestingly, in the early analysis when the data was first published, with about 2 years of follow-up, there didn't look like there was much difference between the acalabrutinib and the acalabrutinib/obinutuzumab arms, although with continued follow up, and we now have out to 5 years, those arms have separated with the antibody combination looking more effective in terms of the PFS.
1:14 | I think, probably because of [COVID-19] coming along, there hasn't been a lot of use of the antibody with acalabrutinib, which is a very effective drug given by itself. But now that—I don't want to say [COVID-19] is gone, but it's more endemic than a pandemic—that would be a real consideration, I think, is using the antibody because of [these] better data in terms of PFS. The one group where the antibody did not seem to add, I will say, are those p53 aberrations, 17p deletions, they both did great with acalabrutinib, but the 2 curves were exactly the same in that subpopulation.