Adding obinutuzumab to ibrutinib among patients with chronic lymphocytic leukemia (CLL) may permit earlier ibrutinib discontinuation, according to research published in Advances in Hematology.
Previous research has shown that ibrutinib, a Bruton tyrosine kinase inhibitor, is effective as a first-line monotherapy in CLL. These results were seen in improved rates in overall response, overall survival, and progression-free survival, leading to the approval of ibrutinib as either a frontline therapy for CLL or for patients unfit for chemotherapy.
There is, however, also evidence that the rate of complete responses (CRs) in this patient population is low. Ibrutinib is, furthermore, linked with both financial toxicity in the United States and a relatively high rate of adverse events, suggesting that earlier discontinuation, where possible, may be an optimal therapeutic strategy.
Obinutuzumab, an anti-CD20 antibody, has previously shown promise as a possible addition to ibrutinib in this setting. For this phase 1b/2 study, researchers evaluated whether adding obinutuzumab to single-agent frontline ibrutinib may lower the rate of infusion reactions and allow patients with CLL to discontinue ibrutinib sooner. All patients with a sustained complete response were permitted to discontinue ibrutinib at 36 months.
Overall, 32 patients were enrolled and treated with combination obinutuzumab and ibrutinib. The median patient age was 66 years, 56% of patients were male sex, 81% of patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, and 59% of patients had del13q cytogenetics.
The overall response rate was 100%, with 28% of patients reaching a CR; 12.5% of patients reached undetectable minimal residual disease in bone marrow. At 3 years, 91% were still in remission, and the overall survival rate was 100%. Among 5 patients who had a sustained CR, ibrutinib discontinuation did not lead to progression.
“Overall, we show that the combination of ibrutinib and obinutuzumab as first-line treatment in CLL patients that either refuse or were considered unsuitable for standard chemoimmunotherapy is safe, is highly effective, and induces deep responses associated with [undetectable minimal residual disease],” the authors wrote.
Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures.
Castro JE, Lengerke-Diaz PA, Velez Lujan J, et al. Ibrutinib plus obinutuzumab as frontline therapy for chronic lymphocytic leukemia is associated with a lower rate of infusion-related reactions and with sustained remissions after ibrutinib discontinuation: a single-arm, open-label, phase 1b/2 clinical trial NCT0231576. Adv Hematol. Published online January 22, 2022. doi:10.1155/2022/4450824