Christine Ryan, MD, hematology/oncology fellow, the Department of Medical Oncology, the Dana-Farber Cancer Institute, discusses the significance of data for ibrutinib (Imbruvica) plus obinutuzumab (Gazyva) in relapsed/refractory chronic lymphocytic leukemia (CLL). 

A phase 1b trial (NCT02537613) investigated potential sequencing options for the combination of ibrutinib and obinutuzumab in patients with relapsed/refractory CLL who have received at least 1 prior line of CLL-directed therapy.

Data shared at the 2022 EHA Congress showed that progression-free survival (PFS) and overall survival rates were similar for all patients treated with the doublet, including those in high-risk subgroups, Ryan says. Among the overall population, the combination elicited a 4-year PFS rate of 74%, Ryan explains.

The findings from the phase 1b study have set the stage for addition evaluation of ibrutinib plus obinutuzumab in relapsed/refractory CLL, Ryan continues. This combination is particularly intriguing because it generated responses in all 3 patients in the phase 1b trial who previously progressed on venetoclax (Venclexta), Ryan concludes.

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Christine Ryan, MD, discusses the significance of data for ibrutinib plus obinutuzumab in relapsed/refractory chronic lymphocytic leukemia. 


Dr. Ryan on the Efficacy of Ibrutinib Plus Obinutuzumab in Relapsed/Refractory CLL

Christine Ryan, MD, hematology/oncology fellow, the Department of Medical Oncology, the Dana-Farber Cancer Institute, discusses the objectives for investigating different sequencing options for ibrutinib (Imbruvica) plus obinutuzumab (Gazyva) in relapsed/refractory chronic lymphocytic leukemia (CLL).

A phase 1b trial (NCT02537613) evaluated different sequencing options for the combination of ibrutinib and obinutuzumab in patients with relapsed/refractory CLL who received at least 1 prior line of CLL-directed therapy.

Safety among patients across all sequencing regimens served as the trial’s primary end point, and secondary end points included overall response rate at 6 and 24 months, plus duration of response and progression-free survival at 24 months, Ryan explains. The rate of undetectable minimal residual disease in the peripheral blood and bone marrow at 6 months was also a key secondary end point, Ryan adds.

Patients were randomized to receive obinutuzumab followed by ibrutinib in arm A, ibrutinib followed by obinutuzumab in arm B, or obinutuzumab plus ibrutinib concurrently in arm C, and dosing mirrored current standard-of-care regimens, Ryan continues. Once patients in all arms started on ibrutinib, the agent was administered daily until disease progression or unacceptable toxicity, Ryan concludes.

Christine Ryan, MD, discusses the objectives for investigating different sequencing options for ibrutinib plus obinutuzumab in relapsed/refractory chronic lymphocytic leukemia.

Dr. Ryan on Objectives for Investigating Ibrutinib Plus Obinutuzumab in R/R CLL

Christine Ryan, MD, hematology/oncology fellow, the Department of Medical Oncology, the Dana-Farber Cancer Institute, discusses the investigation of ibrutinib (Imbruvica) plus obinutuzumab (Gazyva) in relapsed/refractory chronic lymphocytic leukemia (CLL).

Though ibrutinib plus obinutuzumab is approved by the FDA as a frontline therapy for CLL, minimal data have been gathered for the combination in the relapsed/refractory setting, Ryan says. Since ibrutinib monotherapy rarely leads to a complete response in relapsed/refractory CLL, a phase 1b trial (NCT02537613) investigated if the addition of obinutuzumab to ibrutinib could lead to improved efficacy in this treatment setting, Ryan explains.

Along with evaluating the overall efficacy of the combination, the trial tested 3 different sequencing options for obinutuzumab and ibrutinib, Ryan continues. The combination was administered with obinutuzumab prior to ibrutinib in Arm A, and ibrutinib was given prior to obinutuzumab in Arm B. The 2 agents were started together in Arm C, Ryan concludes.

Christine Ryan, MD, discusses the investigation of ibrutinib plus obinutuzumab in relapsed/refractory chronic lymphocytic leukemia.


Christine Ryan, MD

Articles

Dr. Ryan on the Efficacy of Ibrutinib Plus Obinutuzumab in Relapsed/Refractory CLL

Dr. Ryan on Objectives for Investigating Ibrutinib Plus Obinutuzumab in R/R CLL

Dr. Ryan on the Investigation of Ibrutinib Plus Obinutuzumab in Relapsed/Refractory CLL