Behind the ELEVATE-TN Trial of Acalabrutinib/Obinutuzumab in CLL

Jeff Sharman, MD, medical director of hematology research at US Oncology, discusses the background of the ELEVATE-TN trial (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). At the 6-year follow-up mark of the ELEVATE-TN trial, promising safety and efficacy findings were observed.

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0:09 | This was a prospective, randomized, phase 3 study amongst patients with CLL, previously untreated, evaluating 3 different arms. One was sort of a standard chemotherapy, immunotherapy obinutuzumab/chlorambucil, and then there were 2 experimental arms. The first was acalabrutinib monotherapy. The second was acalabrutinib in combination with obinutuzumab.

0:34 | We have previously had our first look at the data with approximately 2 years follow-up. We have subsequently presented both 4- and 5-year follow-up, this now being the 6-year follow-up. But rather than just sort of rehashing the data, we took a number of steps to pick apart the data in ways that we had not previously. The most important finding in this study surrounds the use of obinutuzumab in addition to acalabrutinib. Within the field, there has been a lot of controversy as to whether or not adding obinutuzumab to the [Bruton tyrosine kinase (BTK)] inhibitor and prior studies with rituximab [Rituxan] and ibrutinib [Imbruvica], and other studies kind of turned people off of the idea. This study, however, showed a pretty clinically meaningful and statistically significant improvement for patients who received acalabrutinib if they also received obinutuzumab. We undertook a number of efforts to try to identify which patients might benefit.

1:35 | Most interestingly, we found that any patient who got a complete response had a much longer progression-free survival. And with BTK [inhibitors], that may seem obvious. But for patients treated with BTK inhibitors previously, that has not been demonstrated. We subsequently found that those patients who received an obinutuzumab were much more likely to get a complete response. Those patients with complete response had much better progression-free survival. It's 1 thing to say that a complete response helps. The question is well, who should we be treating with this? The toxicity differences were not too terribly different. There was a little bit 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 unmutated. That did not have a bearing on whether or not patients benefited from acalabrutinib or with the addition of obinutuzumab. Interestingly, though, the patients with deletion 17p, that is the highest risk group in CLL, and we found that those patients did not benefit from the addition of obinutuzumab, so I think it provides some guidance for clinicians to pick and identify who they want to treat with the additional anti-CD20 antibody.