Ibrutinib and Rituximab Improve Progression-Free Survival for Patients with CLL

For patients under the age of 70 with previously untreated chronic lymphocytic leukemia (CLL), the combination of ibrutinib plus rituximab was superior to chemoimmunotherapy, according to new results published at the American Society of Hematology’s annual meeting in Orlando, Florida.

Ibrutinib, a Bruton’s tyrosine kinase inhibitor, and rituximab, an antibody therapy, were superior to chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab (FCR) in boosting patients’ progression-free survival. This means that compared with FCR, ibrutinib and rituximab prolonged the length of time during and after the treatment of CLL that patients lived with the disease without it getting worse. In clinical trials, measuring progression-free survival is a common way to see how well a treatment works, according to the National Cancer Institute (NCI).

The new results support earlier findings that were published in the New England Journal of Medicine, which also found that ibrutinib plus rituximab improved not only progression-free survival, but overall survival as well. Overall survival, according to the NCI, marks the length of time from start of treatment that patients who are diagnosed with a disease are still alive.

“These results are practice-changing and immediately establish ibrutinib and rituximab as the new standard of care for the initial treatment of CLL in patients age 70 and younger,” said Dr Tait Shanafelt, the study’s lead investigator, upon announcement of the preliminary results last year. “The E1912 trial showed that the combination of ibrutinib and rituximab not only provided better leukemia control, it also prolonged life and had fewer side effects.”

In the newest study, Shanafelt and colleagues observed ibrutinib to be well tolerated by the majority of patients, only 14% of whom stopped taking ibrutinib due to its side effects. Moreover, only 7% of patients progressed (or, had worsening disease) while on ibrutinib therapy.

Based on a median follow-up of 48 months, this study reported that 73% of patients in the ibrutinib plus rituximab treatment arm remained on ibrutinib. The only patient characteristic that predicted discontinuation of ibrutinib for a reason other than progression was the number and severity of other health problems patients had in addition to CLL. Among those patients, CLL got worse for less than half, and the median time to progression was about two years.

In the study’s main treatment arm, the median time on treatment was 43 months, or about three and a half years. The median time to progression or death after discontinuing ibrutinib was 23 months, or just under two years.

Superior progression-free survival benefits were sustained for the ibrutinib plus rituximab arm compared to the FCR treatment arm. Overall survival was also determined to be favorable in the ibrutinib plus rituximab arm, compared with patients who underwent FCR.

Less than 7% of patients saw their CLL disease get worse while on therapy, but about 20% of patients in the study discontinued taking ibrutinib for reasons other than progression or death.

Overall, the combination of ibrutinib plus rituximab continues to provide superior progression-free survival compared to FCR for patients with previously untreated CLL.