Jeff P. Sharman, MD, director of research at Willamette Valley Cancer Institute and medical director of hematology research for The US Oncology Network, discusses the challenges of adjusting treatments based on minimal residual disease (MRD) status in high-risk chronic lymphocytic leukemia ​(CLL). 

MRD status is not ready for primetime use in guiding treatment decisions, says Sharman. Moreover, the field does not have robust evidence to suggest that MRD-driven treatment decisions leads to differential outcomes in this patient population.

However, it’s widely understood that patients treated with single-agent BTK inhibitors rarely achieve MRD negativity, Sharman adds. 

Several other treatment​s, such as anti-CD20 antibodies and BCL-2 inhibitors, can elicit MRD negativity,​ says Sharman. Amongst patients treated with BCL-2 inhibitors, it’s now understood that the failure to achieve MRD negativity could correlate with shorter progression-free survival. Additionally, it remains unclear whether continuing BCL-2 inhibitors are beneficial still remain uncertain, Sharman concludes.

Videos

Jeff P. Sharman, MD, discusses the challenges of adjusting treatments based on minimal residual disease status in high-risk chronic lymphocytic leukemia. 

 Dr. Sharman on ​the Challenges of Adjust​ing Treatment Based on MRD Status in CLL

Jeff P. Sharman, MD, director of research at Willamette Valley Cancer Institute and medical director of hematology research for The US Oncology Network, discusses unmet clinical needs in the treatment of patients with high-risk relapsed/refractory chronic lymphocytic leukemia (CLL).

Patients with high-risk CLL, defined by 17p deletions, 

 mutations, or 11q deletions, typically have poor prognosis and inferior progression-free survival compared with patients who don’t have these markers, says Sharman.

However, recent studies suggest that patients with 11q deletions are not as high risk as patients with 17p deletions or 

Although treatment with BTK inhibitors such as ibrutinib (Imbruvica) appear to elicit favorable responses in this patient population, additional research is needed to deliver equally efficacious therapies to all patients with CLL, regardless of risk, Sharman concludes.

Jeff P. Sharman, MD, discusses unmet clinical needs in the treatment of patients with high-risk relapsed/refractory chronic lymphocytic leukemia.



Dr. Sharman on Unmet Clinical Needs in High-Risk Relapsed/Refractory CLL

Jeff P. Sharman, MD, director of research at Willamette Valley Cancer Institute and medical director of hematology research for The US Oncology Network, discusses the results of the phase 3 GENUINE trial in chronic lymphocytic leukemia (CLL).

In GENUINE, investigators evaluated the addition of ublituximab to ibrutinib (Ibruvica) in previously treated patients with high-risk relapsed/refractory CLL. Due to low enrollment, the trial protocol was amended to evaluate overall response rate (ORR) as a primary end point and progression-free survival (PFS) as a secondary end point, says Sharman.

The results, which were presented during the 

, showed a statistically significant improvement in ORR with the addition of ublituximab. Notably, ORR may not be an important end point as it relates to BTK inhibition, which tends to lead to more prolonged responses, explains Sharman. PFS also favored the combination. Patients with 11q deletion, which confers lower risk, did not benefit as much as those with known poor prognostic features, such as 

 mutations and 17p deletions, adds Sharman. GENUINE is the first randomized trial to demonstrate a PFS benefit with the addition of a CD20-directed antibody to ibrutinib. However, the necessity of adding CD20-directed antibodies to BTK inhibitors remains unclear, concludes Sharman.

Jeff P. Sharman, MD, discusses the results of the phase 3 GENUINE trial in chronic lymphocytic leukemia.

Jeff P. Sharman, MD

Articles

Dr. Sharman on the Challenges of Adjusting Treatment Based on MRD Status in CLL

Dr. Sharman on Unmet Clinical Needs in High-Risk Relapsed/Refractory CLL

Dr. Sharman on the Results of the GENUINE Trial in CLL

Jeff P. Sharman, MD

Articles

Dr. Sharman on ​the Challenges of Adjust​ing Treatment Based on MRD Status in CLL

Dr. Sharman on Unmet Clinical Needs in High-Risk Relapsed/Refractory CLL

Dr. Sharman on the Results of the GENUINE Trial in CLL

Dr. Sharman on the Challenges of Adjusting Treatment Based on MRD Status in CLL