Dr. Bhat on the Combination of Ibrutinib Plus FCR in Treatment-Naïve CLL

Seema A. Bhat, MD, a hematologist specializing in chronic lymphocytic leukemia (CLL) at The Ohio State University Comprehensive Cancer Center–James, discusses the combination of ibrutinib (Imbruvica) plus fludarabine, cyclophosphamide, and rituximab (Rituxan; FCR) in young patients with treatment-naïve CLL.

In the phase 3 E1912 study, investigators examined the regimen in the up-front treatment of younger patients with CLL, says Bhat. Ibrutinib was already approved by the FDA for the treatment of patients with CLL in the frontline setting when the E1912 trial began; however, the approval was somewhat controversial, according to Bhat, as the partner arm in the phase 3 RESONATE-2 study received chlorambucil, which is rarely used in young fit patients. The E1912 study compared ibrutinib with the standard of care at the time for younger patients with CLL, which was FCR based on data from the CLL10 study, adds Bhat.

The E1912 study included treatment-naïve patients who were under 70 years; those with high-risk with del(17p) CLL were excluded. In the trial, participants were randomized 2:1 to receive ibrutinib plus rituximab versus FCR given in the standard fashion for 6 cycles. The primary end point of the trial was progression-free survival (PFS), which was met. Ibrutinib plus rituximab significantly improved PFS compared with FCR. Longer follow-up data showed that ibrutinib plus rituximab led to a 3-year PFS rate of 89.4% versus 72.9% with FCR, concludes Bhat.