Paul M. Barr, MD, an associate professor of medicine and director of the Clinical Trials Office at the Wilmot Cancer Institute of the University of Rochester Medical Center, discusses the clinical implications of the long-term results of the phase 3 RESONATE-2 trial (NCT01722487) in chronic lymphocytic leukemia (CLL).

During the 2021 ASCO Annual Meeting, updated findings from the RESONATE-2 trial were presented. The results demonstrated sustained progression-free survival (PFS) and overall survival benefit with frontline ibrutinib (Imbruvica) at a follow-up of up to 7 years in patients with CLL. 

These findings represent the longest follow-up to date from a phase 3 study of first-line BTK inhibitor therapy in CLL , says Barr. Notably, although patients are not yet being cured of their CLL, the long-term disease control that ibrutinib can provide without cumulative or late-onset toxicities is a significant advance in the treatment of patients with this disease, concludes Barr.

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Paul M. Barr, MD, discusses the clinical implications of the long-term results of the phase 3 RESONATE-2 trial in chronic lymphocytic leukemia.



Dr. Barr on the Implications of the Long-Term Results of the RESONATE-2 Trial in CLL 

Paul M. Barr, MD, an associate professor of medicine and director of the Clinical Trials Office at the Wilmot Cancer Institute of the University of Rochester Medical Center, discusses exploring umbralisib (TGR-1202) plus ublituximab (TGTX-1101; U2) plus venetoclax (Venclexta) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL).

Findings from a multicenter, phase 1/2 study, which were presented virtually during the 2020 ASH Annual Meeting & Exposition, demonstrated encouraging efficacy and a manageable safety profile among patients with relapsed/refractory disease. In the trial, patients received 3 cycles of U2 followed by 400 mg of venetoclax, which was continued for 9 cycles. Notably, ublituximab is a novel glycoengineered CD20-directed monoclonal antibody, and umbralisib is a small molecule inhibitor that targets PI3Kδ and CK1ε, Barr says.

 Within the first 3 cycles of U2, all patients responded, including those who were previously relapsed/refractory to a BTK inhibitor. Moreover, the combination decreased tumor burden and effectively reduced the risk of tumor lysis syndrome for these patients, Barr concludes.

Paul M. Barr, MD, discusses exploring umbralisib plus ublituximab plus venetoclax in patients with relapsed/refractory chronic lymphocytic leukemia. 

Dr. Barr on Exploring U2 Plus Venetoclax in Relapsed/Refractory CLL 

Paul Barr, MD, medical director, Cancer Center Clinical Trials Office, and assistant professor, School of Medicine and Dentistry, University of Rochester, discusses the 6-year follow-up in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) on ibrutinib (Imbruvica) as part of the RESONATE study.

This phase III study randomized patients to receive oral ibrutinib 420 mg daily until or intravenous ofatumumab (Arzerra) for up to 24 weeks. Of the 391 patients randomized to receive ibrutinib (n = 195) or ofatumumab (n = 196), 86% and 79%, respectively, were in the genomic high-risk population. Of patients randomized to ofatumumab, 68% switched to ibrutinib.

Patients with unmutated IGHV status seem to respond to ibrutinib just as well as patients with mutated 

 status, according to Barr. Patients with other high-risk features, such as 11q deletion, 17p deletion, and 

 mutations responded nearly as well as patients with more favorable risk factors. Patients with 11q deletion responded exceptionally well with a median PFS approaching 60 months. Overall, patients on the ibrutinib arm had a median PFS of 44.1 months. Approximately, 40% of patients are without progression and still alive after five years.

The RESONATE study helped researchers understand how durable the responses to ibrutinib are in this patient population, according to Barr. After 6 years of follow-up, extended ibrutinib treatment showed sustained efficacy in patients with relapsed/refractory CLL, including patients with high-risk genomic features. These results demonstrate long-term benefit and tolerability for continuous ibrutinib treatment in patients with relapsed/refractory CLL.

Paul Barr, MD

Articles

Dr. Barr on the Implications of the Long-Term Results of the RESONATE-2 Trial in CLL

Dr. Barr on Exploring U2 Plus Venetoclax in Relapsed/Refractory CLL

Dr. Barr on Updated RESONATE Data in IGHV-Mutant CLL