In patients with previously untreated chronic lymphocytic leukemia (CLL), the interim results of the phase 3 ELEVATE-TN trial have revealed that acalabrutinib (Calquence®, AstraZeneca) improves progression-free survival, either as monotherapy or in combination with obinutuzumab (Gazyva®, Genentech). This study led to the recent FDA approval of acalabrutinib for CLL and small lymphocytic lymphoma (SLL). In this interview with i3 Health, Jeff P. Sharman, MD, the trial's principal investigator, discusses ELEVATE-TN's results, which he will be presenting today at the American Society of Hematology (ASH) Annual Meeting and Exposition.
What was the study's aim, and what was the trial design?
Jeff P. Sharman, MD: This study was designed to enable FDA approval of acalabrutinib for previously untreated patients with CLL/SLL. It was a three-arm study comparing acalabrutinib with or without obinutuzumab to chlorambucil/obinutuzumab. Eligible patients were 65 years or older, or they were younger than 65 with comorbidities that precluded more intensive treatment. Patients were followed for progression-free survival.
What were your findings, and what impact did they have?
Dr. Sharman: Both acalabrutinib arms (with or without obinutuzumab) significantly outperformed the control arm. On November 21, 2019, acalabrutinib was approved by the FDA and by several other countries for patients with CLL/SLL.
Can you comment on the larger significance of your results?
Dr. Sharman: This study extends the literature confirming the safety and efficacy of Bruton's tyrosine kinase (BTK) inhibitors in patients with previously untreated CLL. Furthermore, it is the first to show an improvement in outcome associated with the addition of an anti-CD20 antibody. This differs from multiple prior studies that have looked at first-generation anti-CD20 therapies.
What additional follow-up research is needed?
Dr. Sharman: This study raises questions about whether the differences in outcomes with the anti-CD20 therapy are attributable to the unique BTK agent or anti-CD20 agent utilized. Those are questions and answers beyond the scope of this trial.
What advice can you give to community hematologist-oncologists treating patients with CLL?
Dr. Sharman: The treatment landscape for frontline CLL has exploded in the last 24 months. With new data for BTK inhibitors versus the main frontline chemoimmunotherapy regimens––FCR (fludarabine/cyclophosphamide/rituximab), BR (bendamustine/rituximab), and chlorambucil/obinutuzumab––and BCL-2 inhibitors versus chlorambucil/obinutuzumab, treatment selection has been dramatically altered. Understanding which regimen is right for an individual patient now involves multiple new data sets to be considered. It is no longer suitable for physicians to revert to comfortable or familiar treatment choices.
About Dr. Sharman
Jeff P. Sharman, MD, is Director of Research at Willamette Valley Cancer Institute and is Medical Director of Hematology Research for the US Oncology Network. He has led a number of clinical trials, many of which have investigated treatments for CLL. He has published his research in the New England Journal of Medicine, the Journal of Clinical Oncology, Blood, and other peer-reviewed journals.
For More Information
Sharman JP, Banerji V, Fogliatto LM, et al (2019). ELEVATE TN: phase 3 study of acalabrutinib combined with obinutuzumab (O) or alone vs O plus chlorambucil (Clb) in patients (Pts) with treatment-naive chronic lymphocytic leukemia (CLL). 61st American Society of Hematology Annual Meeting & Exposition. Abstract 31.
Transcript edited for clarity. Any views expressed above are the speakers' own and do not necessarily reflect those of i3 Health.