Imbruvica And Rituxan Bests Standard-of-Care Regimen in Patients With Previously Untreated CLL

The data demonstrated that the combination of Imbruvica and Rituxan conferred superior progression-free survival results in patients with previously untreated chronic lymphocytic leukemia, compared with the chemotherapies fludarabine and cyclophosphamide plus Rituxan.

The use of Imbruvica (Ibrutinib) plus Rituxan (rituximab) elicited superior progression-free survival (or the time during and after treatment when the patient lives without disease progression) compared with the chemoimmunotherapy combination of fludarabine, cyclophosphamide, and Rituxan (FCR) in patients with previously untreated chronic lymphocytic leukemia (CLL).

The results, which were presented at the 2021 ASH Annual Meeting an Exposition, demonstrated that at a median follow-up of 52.7 months, a median progression-free survival was not met with Imbruvica and Rituxan versus 66.53 months with FCR.

Progression-free survival was also significantly better with Imbruvica and Rituxan in patients with IGHV unmutated CLL, 11q deletion, and normal karyotype but not for patients with IGHV mutated CLL at follow-up.

The trial included 771 patients (73.3% are male; median age, 62 years) from 113 United Kingdom-based centers who were enrolled onto trial between Sept. 19, 2014, and July 19, 2018. Patients who were aged over 75 years and had a more than 20% presence of 17p-deleted cells were excluded. Secondary endpoints included overall survival (or the time from diagnosis or treatment start when patients are alive), attainment of undetectable minimal residual disease (MRD), response to therapy, safety and toxicity, health-related quality of life and cost-effectiveness.

Patients received either six cycles of FCR (385 patients) every 28 days or Imbruvica plus Rituxan for up to six years with stratification by disease stages, age, gender, and center.

A total of 59 and 21 patients received second-line treatment after FCR and Imbruvica plus Rituxan, respectively, and 88.1% of patients received targeted therapies for CLL progression after FCR.

At a median follow-up of 50.2 months, overall survival was not different between the two regimens with 29 deaths in the FCR group (four from CLL, three from Richter’s, three AML/MDS, three COVID-19 and two cardiac/sudden) and 30 in the Imbruvica plus Rituxan group (three from CLL, one from Richter’s, three COVID-19 and eight cardiac/sudden).

“There is no difference in overall survival, but almost all patients relapsing after FCR received either (Imbruvica) or (Venclexta) plus (Rituxan),” the researchers wrote in the presentation.

Of note, four-year overall survival significantly improved with FCR in this trial at 94.5%, compared with 84.2% in other trials that were published between 2009 and 2012.

The researchers highlighted results from the ADMIRE and ARCTIC trials, both of which had the same inclusion criteria, centers, and an identical FCR schedule, however those were conducted prior to the availability of targeted therapies in the relapse setting.

At three months post treatment, 233 patients (60.5%) in the FCR group and 81 (21%) in the Imbruvica plus Rituxan group achieved a complete response, 106 (27.6%) and 271 (70.2%) achieved a partial response, respectively, and 46 (11.9%) and 34 (8.8%) had either stable disease, progressive disease or no response.

Overall, a greater percentage of patients in the FCR group (55.3%) became MRD negative, meaning no traces of disease were detected after treatment, via tests of the bone morrow at three months post-treatment compared with the Imbruvica and Rituxan group (3.9%).

Serious side effects occurred in 53.7% and 53.4% of patients in FCR and Imbruvica plus Rituxan groups, respectively. Differences in serious side effects by organ class for FCR versus Imbruvica plus Rituxan were 33.6% versus 27.1%; blood and lymphatic in 19.8% vs 10.7%; and cardiac in 1.1% vs 8.3%, respectively.

Ten deaths, eight of which occurred in the Imbruvica and Rituxan group, were attributed to sudden or cardiac events. Further analysis, according to the authors, identified that seven of the deaths that occurred in the Imbruvica and Rituxan group were in patients who had a history of hypertension or cardiac disease, whereas the patients who accounted for the two deaths in the FCR arm did not have a history of either condition.

A version of this article was originally published on OncLive as, “Ibrutinib Plus Rituximab Confers Superior PFS to FCR in Previously Untreated CLL.”

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