Background to the ELEVATE-TN study on acalabrutinib/obinutuzumab in CLL

Jeff Sharman, MD, medical director of hematology research at US Oncology, explains the background of the ELEVATE-TN study (NCT02475681) and its long-term efficacy data.

The study evaluated acalabrutinib (Calquence) with or without obinutuzumab (Gazyva) in patients with treatment-naive chronic lymphocytic leukemia (CLL). After 6 years of follow-up of the ELEVATE-TN study, promising results were observed regarding safety and efficacy.

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0:09 | This was a prospective, randomized phase 3 trial in patients with CLL who had been previously untreated. It looked at three different arms. One was a type of standard chemotherapy, the immunotherapy obinutuzumab/chlorambucil, and then there were two experimental arms. The first was acalabrutinib monotherapy. The second was acalabrutinib in combination with obinutuzumab.

0:34 | We already looked at the data for the first time at about 2 years of follow-up. We then presented both 4- and 5-year follow-up, with this now being the 6-year follow-up. But rather than just rehashing the data, we took a number of steps to tease apart the data in a way that we had not done before. The most important finding of this study concerns the use of obinutuzumab in addition to acalabrutinib. There has been a lot of controversy within the field about whether the addition of obinutuzumab to [Bruton tyrosine kinase (BTK)] Inhibitor and previous studies with rituximab [Rituxan] and ibrutinib [Imbruvica]and other studies have scared people away from the idea. But this study showed a pretty clinically meaningful and statistically significant improvement for patients who received acalabrutinib when they also received obinutuzumab. We did a number of trials to figure out which patients might benefit.

1:35 | What was particularly interesting was that all patients who showed a complete remission had a much longer progression-free survival. And with BTK [inhibitors]that may seem obvious. But for patients previously treated with BTK inhibitors, that has not been demonstrated. We later found that patients who received obinutuzumab were much more likely to have a complete remission. Patients who had a complete remission had a much better progression-free survival. It's one thing to say that a complete remission helps. Now the question is, who should we treat with it? The differences in toxicity were not too great. There was a little more neutropenia with the addition of obinutuzumab.

2:21 | But we looked at certain molecular risk groups; we looked at IGHV Mutation status, both mutated and non-mutated. This did not affect whether patients benefited from acalabrutinib or from the addition of obinutuzumab. Interestingly, patients with deletion 17pthat's the highest risk group in CLL, and we found that those patients did not benefit from the addition of obinutuzumab. So I think that provides some guidance for clinicians to select and determine who they want to treat with the additional anti-CD20 antibody.