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Videos

Dr. John F. Seymour presents preliminary results from the Phase 1 CaDAnCe-101 study, highlighting the efficacy and safety of the BTK degrader BGB-16673 in relapsed or refractory Waldenström macroglobulinemia, demonstrating high response rates, rapid improvements in cytopenias, and promising activity across diverse mutation profiles.

Preliminary Efficacy and Safety of the Bruton Tyrosine Kinase Degrader BGB-16673 in Patients With Relapsed or Refractory Waldenström Macroglobulinemia: Results From the Phase 1 CaDAnCe-101 Study

John F. Seymour, M​BBS, FRACP, PhD, director, ​Integrated Haematology Department, clinical hematologist, associate director of Clinical Research, Peter MacCallum Cancer Centre, Victoria Australia, discusses the design of the phase 3 ELEVATE-RR trial (NCT02477696) comparing acalabrutinib (Calquence) vs ibrutinib (Imbruvica) in chronic lymphocytic leukemia (CLL).

The design of the ELEVATE-RR trial followed the format of a nonblinded study in which patients with previously treated, high-risk CLL were randomized 1:1 to ibrutinib or acalabrutinib, Seymour says. Moreover, regarding dosing of the oral BTK inhibitors, acalabrutinib was given at 100 mg twice daily, and ibrutinib was given at 420 mg once daily, Seymour explains.

Additionally, the primary end point of the trial was noninferiority by independent review committee–assessed progression-free survival, Seymour continues. Several prespecified secondary end points were included, including the incidence of any-grade atrial fibrillation or flutter, which is a recognized toxicity with BTK inhibitors, Seymour concludes.

John F. Seymour, M​BBS, FRACP, PhD, discusses the design of the phase 3 ELEVATE-RR trial comparing acalabrutinib vs ibrutinib in chronic lymphocytic leukemia. 


Dr. Seymour on the Design of the ELEVATE-RR Trial in Relapsed/Refractory CLL 

John F. Seymour, MBBS, PhD, clinical hematologist, associate director of Clinical Research, Peter MacCallum Centre, director of the integrated Haematology Department of the Peter MacCallum Cancer Centre and the Royal Melbourne Hospital, discusses the 4-year update of the phase III MURANO trial in chronic lymphocytic leukemia (CLL).

View more from the 2019 ASH Annual Meeting

Dr. Seymour on the 4-Year Update of the MURANO Trial in CLL

John F. Seymour, MBBS, PhD, clinical hematologist, associate director of Clinical Research, Peter MacCallum Centre, director of the integrated Haematology Department of the Peter MacCallum Cancer Centre and the Royal Melbourne Hospital, discusses the rationale for the MURANO study in patients with chronic lymphocytic leukemia (CLL).

Novel agents have shown promise in this space, particularly venetoclax, a BCL2 inhibitor, says Seymour, but also BTK inhibitors and PI3 kinase inhibitors. The challenge with these drugs as single agents is that they have to be given continuously until disease progression. This is because the complete remission rate and minimal residual disease (MRD) negativity is relatively low. In order to bring patients off therapy, physicians need to see MRD negativity.

The combination of venetoclax and rituximab (Rituxan) has been known to achieve MRD negativity, so the MURANO trial tested this against the standard 6 cycles of bendamustine and rituximab in a time-limited fashion for patients with relapsed/refractory CLL. In updated data presented at the 2018 ASH Annual Meeting, patients treated with venetoclax had higher progression-free survival and MRD negativity rates.

John F. Seymour, MBBS, PhD, clinical hematologist, associate director of Clinical Research, Peter MacCallum Centre, director of the integrated Haematology Department of the Peter MacCallum Cancer Centre and the Royal Melbourne Hospital, discusses the rationale for the MURANO study in patients with chronic lymphocytic leukemia.

Dr. Seymour Discusses Rationale for MURANO Study in CLL

John F. Seymour, MBBS, PhD, clinical hematologist, associate director of Clinical Research, Peter MacCallum Centre, director of the integrated Haematology Department of the Peter MacCallum Cancer Centre and the Royal Melbourne Hospital, discusses the updated findings from the MURANO trial presented at the 2018 ASH Annual Meeting.

 established the superiority of the combination of venetoclax (Venclexta) and rituximab (Rituxan) as treatment for patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Data favored the venetoclax combination compared with bendamustine plus rituximab in terms of progression-free survival (PFS), and patients treated with venetoclax showed higher rates of undetectable minimal residual disease (MRD). This updated analysis focused on patients on the venetoclax/rituximab arm after drug cessation, says Seymour.

At a nearly 12-month median follow-up, all patients—regardless of MRD status&mdash;who stopped venetoclax at the 2-year mark had an 87% likelihood of PFS. As a general treatment strategy, time-limited therapy with drug cessation is feasible and safe, says Seymour. Although progression was seen in some patients with high MRD positivity, upon further investigation, data showed that they were progressing on venetoclax prior to cessation, Seymour explains.

John F. Seymour, MBBS, PhD

Articles

Preliminary Efficacy and Safety of the Bruton Tyrosine Kinase Degrader BGB-16673 in Patients With Relapsed or Refractory Waldenström Macroglobulinemia: Results From the Phase 1 CaDAnCe-101 Study

Dr. Seymour on the Design of the ELEVATE-RR Trial in Relapsed/Refractory CLL

Dr. Seymour on the 4-Year Update of the MURANO Trial in CLL

Dr. Seymour Discusses Rationale for MURANO Study in CLL

Dr. Seymour on Updated Findings From the MURANO Trial in CLL