At the 65th ASH Annual Meeting, in San Diego, California, Jeff Sharman, MD, Willamette Valley Cancer Institute, Eugene, Oregon, presented findings from a 6-year follow-up of the ELEVATE-TN (NCT02475681) trial, which indicated that acalabrutinib with or without obinutuzumab continued to yield promising efficacy outcomes among patients with treatment-naive (TN) chronic lymphocytic leukemia (CLL), including those with high-risk features. 

Transcript: 

Hi, my name is Jeff Sharman. I'm a hematologist and oncologist and I practice in Eugene, Oregon. I serve as the medical director of hematology research for Sarah Cannon Research Institute and the US Oncology Network. At ASH 2023, we have the opportunity to present a long-term follow-up of the ELEVATE-TN study. This was a 3-arm study looking at the outcome for patients with untreated CLL receiving either the standard control arm---obinutuzumab, chlorambucil---or acalabrutinib with or without obinutuzumab. It was a 3-arm study, acalabrutinib, acalabrutinib-obinutuzumab, or control chemoimmunotherapy. This is a study that led to the FDA approval of acalabrutinib in the frontline setting. For patients with previously untreated CLL, this was the study that led to the approval of the agent. We've previously given reports at roughly 2 years, 4 years, [and] 5 years. This is now looking at the 6-year follow-up.

What's particularly interesting about this dataset is, within the field of CLL, the role of obinutuzumab in combination with [Bruton’s tyrosine kinase] (BTK) inhibitors is somewhat uncertain. There have been a variety of studies where the addition of anti-CD20 antibody did not provide a benefit. This study shows that obinutuzumab in combination with acalabrutinib has a very impressive outcome. At 6 years, we have almost 4 out of 5 patients who still remain free from progression at the 6-year mark---78%. That difference was actually 16% higher than acalabrutinib monotherapy. So, it does appear that obinutuzumab provides benefit over acalabrutinib alone. 

We dove into that data a little bit further to try to figure out who and why. We saw that the benefit of obinutuzumab did extend to those patients with [immunoglobulin heavy chain variable region] (IGHV)-mutated or unmutated. We looked at individuals with high-risk disease with deletion of 17p and interestingly in that group, the 17p or the TP53  mutated patients did not get benefit from the obinutuzumab, with a hazard ratio of 2.9. It does look like the addition of obinutuzumab provides considerable benefit over acalabrutinib monotherapy. That's true whether you have IGHV-mutated/unmutated, but not the 17p. 

Finally, we looked at the impact on response rates. In particular, those patients who received obinutuzumab had higher rates of complete responses. If you took the 2 arms that contained acalabrutinib and combined them and asked the question, does a complete response rate matter? The answer is actually a strong yes, which is different from what we had understood previously. Previously in the field, we didn't know the value of complete responses, but what this study shows is that getting patients all the way to a complete response rate has a significant impact on their progression-free survival. Those are the take-home points from this presentation and thank you for letting me share it with you.

Source: 

Sharman J, Egyed M, Jurczak W, et al. Acalabrutinib ± obinutuzumab vs obinutuzumab + chlorambucil in treatment-naive chronic lymphocytic leukemia: 6-year follow-up of elevate-TN.  Presented at the ASH 65th Annual Meeting & Exposition; December 9-12 2023; San Diego, California. Abstract 636