Jeff Sharman, MD, director of research, the Willamette Valley Cancer Institute, medical director of hematology research, The US Oncology Network, discusses 5-year follow-up data from the phase 3 Elevate CLL TN trial (NCT02475681) in treatment-naïve patients with chronic lymphocytic leukemia (CLL).

The Elevate CLL TN study investigated the efficacy of acalabrutinib (Calquence) monotherapy vs acalabrutinib plus obinutuzumab (Gazyva) vs obinutuzumab plus chlorambucil in patients with previously untreated CLL. A 5-year updated analysis was performed to determine the long-term benefits of the 3 regimens studied.

Initial findings from the Elevate CLL TN trial showed that the acalabrutinib-containing arms showed superiority over the obinutuzumab plus chlorambucil arm in terms of efficacy and safety, Sharman says. At 5 years, the acalabrutinib arms continue to demonstrate a progression-free survival benefit vs obinutuzumab plus chlorambucil, Sharman explains.

These follow-up data also show an overall survival (OS) benefit for acalabrutinib plus obinutuzumab vs obinutuzumab plus chlorambucil, Sharman notes. Acalabrutinib monotherapy also seems promising, but has not yet shown an OS benefit, Sharman concludes.

Videos

Jeff Sharman, MD, discusses 5-year follow-up data from the phase 3 Elevate CLL TN trial in treatment-naïve patients with chronic lymphocytic leukemia.

Dr. Sharman on 5-Year Data From the Elevate CLL TN Trial in CLL

Jeff Sharman, MD, director of research at Willamette Valley Cancer Institute and medical director of hematology research for The US Oncology Network, discusses the question of BTK inhibitors in treating patients with chronic lymphocytic leukemia.

Data from the phase III ELEVATE-TN trial, along with the data from the phase III ASCEND trial, led to the FDA’s decision to approve the use of acalabrutinib (Calquence) for the treatment of patients with CLL or small lymphocytic lymphoma. Acalabrutinib has also received regulatory approval in Canada and Australia in this space, according to Sharman.

Now, the big challenge faced in the field is determining which BTK inhibitor to prescribe, says Sharman. To this end, an ongoing randomized trial comparing the BTK inhibitors head-to-head and will potentially provide more pivotal information regarding their safety and efficacy.

Until those data read out, becoming familiar with the inhibitors that are available is strongly encouraged, says Sharman, as doing so could help determine how to select the most appropriate treatment for each patient.

Jeff Sharman, MD, discusses the question of BTK inhibitors in treating patients with chronic lymphocytic leukemia.

Dr. Sharman on Remaining Challenges With BTK Inhibitors in CLL

Jeff Sharman, MD, director of research at Willamette Valley Cancer Institute and medical director of hematology research for The US Oncology Network, discusses the design of the phase III ELEVATE-TN trial in patients with previously untreated chronic lymphocytic leukemia (CLL).

The trial enrolled patients ≥65 years of age or those <65 years of age with medical comorbidities that made them eligible for a less intensive chemoimmunotherapy regimen. The 3-arm study evaluated acalabrutinib (Calquence) alone or in combination withobinutuzumab (Gazyva) versus obinutuzumab/chlorambucil.

The primary endpoint was progression free survival (PFS) in the acalabrutinib/obinutuzumab arm versus the obinutuzumab/chlorambucil arm. Secondary endpoints included PFS in the acalabrutinib-alone arm versus obinutuzumab/chlorambucil, as well as safety, time to next treatment, and overall survival (OS).

The median PFS was not reached with either acalabrutinib arm. However, the PFS in the chlorambucil/obinutuzumab arm was 22.6 months (95% CI, 20.2-27.6). The 2-year PFS rates were 93%, 87%, and 47% for acalabrutinib/obinutuzumab, acalabrutinib monotherapy, and obinutuzumab/chlorambucil, respectively.

The OS in the acalabrutinib monotherapy arm (HR, 0.60; 95% CI, 0.28-1.27; 

 = .1556) was better than the acalabrutinib/obinutuzumab arm (HR, 0.47; 95% CI, 0.21-1.06; 

 = .0577; however, the benefit was not statistically significant. The 2-year OS rates were 95%, 95%, and 92% with acalabrutinib/obinutuzumab, acalabrutinib monotherapy, and obinutuzumab/chlorambucil, respectively.

Jeff Sharman, MD, discusses the design of the phase III ELEVATE-TN trial in patients with previously untreated chronic lymphocytic leukemia.
 

Dr. Sharman on the Design of the ELEVATE-TN Trial in CLL

Jeff Sharman, MD, director of research at Willamette Valley Cancer Institute and medical director of hematology research for The US Oncology Network, discusses the potential future roles of acalabrutinib (Calquence) in chronic lymphocytic leukemia (CLL).

Acalabrutinib is not currently approved for patients with CLL, but Sharman believes that could change with 3 pivotal studies. At the 2019 European Hematology Association Congress, data from the phase III ASCEND trial showed the superiority of acalabrutinib monotherapy to bendamustine/rituximab (Rituxan) and idelalisib (Zydelig)/rituximab in the relapsed/refractory setting. Sharman believes these results will lead to the FDA approval of acalabrutinib in the relapsed/refractory setting.

Additionally, a press release stated that the combination of acalabrutinib and obinutuzumab (Gazyva) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus obinutuzumab/chlorambucil in patients with treatment-naive CLL, meeting the primary endpoint of the phase III ELEVATE-TN trial. Moreover, single-agent acalabrutinib showed a statistically significant and clinically meaningful improvement in PFS versus obinutuzumab/chlorambucil, which was a secondary endpoint. The full findings have not been released yet, but Sharman anticipates acalabrutinib could receive regulatory approval in the frontline setting. 

Jeff Sharman, MD, director of research at Willamette Valley Cancer Institute and medical director of hematology research for The US Oncology Network, discusses the potential future of acalabrutinib (Calquence) in chronic lymphocytic leukemia (CLL). 

Dr. Sharman on the Potential Future of Acalabrutinib in CLL

Jeff Sharman, MD, medical director, Hematology Research, The US Oncology Network, discusses the phase III findings of the GENUINE study, the combination of ublituximab (TG-1101) and ibrutinib (Imbruvica) for patients with previously treated high-risk chronic lymphocytic leukemia (CLL).

View more from the 2017 ASCO Annual Meeting

Dr. Sharman on the Phase III Results of the GENUINE Study in CLL

Jeff Sharman, MD, director of Research with Willamette Valley Cancer Institute and Research Center, medical director of Hematology Research for The US Oncology Network, discusses clinical activity of entospletinib in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) who were previously treated with a B-cell receptor pathway signaling inhibitor.

Entospletinib is a SYK inhibitor, Sharman explains. SYK is one member of the downstream signaling pathway of the B-cell receptor, in which other targets include BTK and PI3K delta. Agents such as ibrutinib and idelalisib are already used in this space, but this third agent targets another portion of the pathway, he adds.

Substantial activity with entospletinib has been observed in patients in an ongoing study. High levels of response and prolonged disease control have also been demonstrated. Reported toxicities, which include liver function test abnormalities, have been manageable, Sharman says.

Jeff Sharman, MD, director of Research with Willamette Valley Cancer Institute and Research Center, medical director of Hematology Research for The US Oncology Network, discusses clinical activity of entospletinib in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) who were previously treated with a B-cell receptor pathway signaling inhibitor. 


Jeff Sharman, MD

Articles

Dr. Sharman on 5-Year Data From the Elevate CLL TN Trial in CLL

Dr. Sharman on Remaining Challenges With BTK Inhibitors in CLL

Dr. Sharman on the Design of the ELEVATE-TN Trial in CLL

Dr. Sharman on the Potential Future of Acalabrutinib in CLL

Dr. Sharman on the Phase III Results of the GENUINE Study in CLL

Dr. Sharman on Entospletinib in Patients With CLL