Exploring Acalabrutinib Plus or Minus Obinutuzumab for CLL in the ELEVATE-TN Study With Jeff Sharman, MD
Recently, at the American Society of Hematology (ASH) Annual Meeting, Dr. Jeff P. Sharman, the Medical Director of Hematology Research for Sarah Cannon Research Institute and the US Oncology Network, presented the long-term follow up results from the ELEVATE-TN study, which investigated acalabrutinib plus or minus obinutuzumab for previously untreated patients with chronic lymphocytic leukemia (CLL). Prior to his presentation, he sat down with Oncology Data Advisor to discuss the study, the results, and how this could affect the future treatment landscape for patients with CLL.
Oncology Data Advisor: Welcome to Oncology Data Advisor. Today, we're here with Dr. Jeff Sharman. Thank you so much for your time today. Would you like to begin with introducing yourself and your research interests?
Jeff Sharman, MD: Happy to do so. My name is Jeff Sharman. I'm a Hematologist-Oncologist at the Willamette Valley Cancer Institute in Eugene, Oregon. I serve as the Medical Director of Hematology Research for Sarah Cannon and the US Oncology Network. My research interest has historically been within lymphoid malignancies, and in particular I've been involved in a lot of therapeutic development in lymphomas and chronic lymphocytic leukemia where I've done the majority of my work.
Oncology Data Advisor: Could you tell us a bit about what you will be presenting today?
Dr. Sharman: This evening, I'll be presenting an oral session looking at long-term follow up of the ELEVATE-TN study, which is for previously untreated patients with chronic lymphocytic leukemia. This was a randomized, three-arm, phase 3 study in which patients received either a standard chemo-immunotherapy, obinutuzumab/chlorambucil, or they received acalabrutinib monotherapy or acalabrutinib in combination with obinutuzumab. We are now presenting the six-year follow-up—median 72 months. What we are able to demonstrate is that the progression-free survival for the combination of acalabrutinib/obinutuzumab is 78%, and for acalabrutinib monotherapy, it's 62%.
The significance to the field of this is, number one, this led to the approval of acalabrutinib in previously untreated CLL patients. Number two, it addresses an area in the literature that has been subject of uncertainty, which is what's the proper role of anti-Cd20 antibodies in combination with Bruton tyrosine kinase (BTK) inhibitors. We had several novel insights into that question as part of this presentation. We found that obinutuzumab provides clinical benefit to those patients who have either an immunoglobulin heavy-chain variable region gene (IGHV)–mutated or unmutated disease—both groups benefited. We found that patients with deletion 17P did not derive additional benefit from the addition of obinutuzumab.
Then finally, we identified that those individuals who obtained a complete response from either acalabrutinib monotherapy or acalabrutinib in combination with obinutuzumab had a significantly improved outcome relative to those who didn't have a complete response. While that may sound intuitive, that's not something that was actually recognized by the field, and in fact, it previously was thought largely that getting a complete response rate didn't matter. But our findings actually dispute that finding and point to the importance of a complete response, which is much more common amongst those individuals who are treated with obinutuzumab in addition to their acalabrutinib.
Oncology Data Advisor: Could you tell us a bit about your team's goals and future planning regarding this research area?
Dr. Sharman: With regards to this study, one of the biggest questions right now in CLL is, what is the optimal front-line therapy? In general, there's a fixed duration strategy utilizing venetoclax in combination with obinutuzumab, and there's a continuous strategy in which patients receive a BTK inhibitor with or without obinutuzumab. I think that there is a goal to move towards a fixed duration therapy. The question then is, "What's the right doublet or triplet of medications to get us there?" So far, I think the field is agreeing that doublets probably are an improvement over single-agent therapy; however, which is the optimal doublet remains to be seen. That will be subject to some of our other studies that we're conducting right now, such as the MAJIC study, which randomly assigns patients to either venetoclax with acalabrutinib or venetoclax in combination with obinutuzumab. We're testing what's the optimal partner for venetoclax, a BTK inhibitor or an anti-CD20 antibody.
About Dr. Sharman
Jeff P. Sharman, MD, is the Medical Director of Hematology Research for Sarah Cannon Research Institute and the US Oncology Network. He is also a Hematologist-Oncologist at the Willamette Valley Cancer Institute in Eugene, Oregon. Dr. Sharman's research interest revolves around lymphoid malignancies, including therapeutic development in lymphomas and CLL. He has led a number of clinical trials, many of which have investigated treatments for CLL.
For More Information
Sharman J, Egyed M, Jurczak W, et al (2023). Acalabrutinib ± obinutuzumab vs obinutuzumab + chlorambucil in treatment-naive chronic lymphocytic leukemia: 6-year follow-up of Elevate-TN. Presented at: 2023 American Society of Hematology Annual Meeting. Abstract 636. Available at: https://ash.confex.com/ash/2023/webprogram/Paper174750.html
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor.