Phase Ib/II Clinical Trial: Does Regimen Treatment for CLL Reduce Infusion-Related Reactions?

By: Victoria Kuhr, BA
Posted: Thursday, March 24, 2022

The monoclonal antibody obinutuzumab in combination with the Bruton’s tyrosine kinase ibrutinib as a front-line treatment appears to be safe and effective for patients with chronic lymphocytic leukemia (CLL) who are unfit for other treatments. Thomas J. Kipps, MD, PhD, of the Chronic Lymphocytic Leukemia Research Consortium and Moores Cancer Center, California, and colleagues reported that the combination therapy was associated with a lower rate of infusion-related reactions. The phase Ib/II study findings were published in Advances in Hematology.

“Treatment of ibrutinib and the IG-regimen [ibrutinib plus obinutuzumab] was associated with a lower rate of abrogation in the release of associated cytokines/chemokines and sustained remissions despite ibrutinib discontinuation in patients,” said the authors.

This single-arm study enrolled therapy-naive adults with CLL requiring treatment by the International Workshop on Chronic Lymphocytic Leukemia 2008 criteria. Patients had a performance status of 2 or less and normal renal and hepatic function. All patients received oral ibrutinib (420 mg once daily, started 1 hour before antibody infusion) plus obinutuzumab. The combination therapy was administered until disease progression, unacceptable toxicity, or another reason for treatment discontinuation.

The initial six patients included in the phase Ib analysis showed no dose-limiting toxicity. Therefore, 26 additional patients were enrolled in the phase II study. All patients completed the six planned cycles of obinutuzumab.

At a median follow-up of 35.5 months, 13 patients (41%) discontinued ibrutinib. The median time to ibrutinib discontinuation was 35 months. During the initial 18 months of follow-up, three patients (9%) discontinued ibrutinib due to grade 2 atrial fibrillation and grade 1 to 2 skin rash. Infusion-related reactions of any grade occurred in 19% of patients, and grade 3 or 4 ibrutinib-related reactions occurred in 3% of patients. The overall infusion-related reaction rate was 19% versus 65% (ibrutinib plus obinutuzumab vs. obinutuzumab plus chlorambucil).

Disclosure: For full disclosure of study authors, visit www.hindawi.com.

Advances in Hematology