Ibrutinib Superior to Chemoimmunotherapy in Treatment-Naive CLL

Treatment with ibrutinib for chronic lymphocytic leukemia (CLL) resulted in a favorable benefit/risk profile for patients with treatment-naive disease and could potentially eliminate the need for chemotherapy in some patients, according to the results of a cross-trial comparison.

“In this cross-trial analysis of first-line regimens, with median follow-up ranging from to 14.5–37.4 months, single-agent ibrutinib appeared to be associated with longer progression-free survival relative to published phase III data for chemoimmunotherapy,” Tadeusz Robak, MD, PhD, of the Medical Univeristy of Lodz, and colleagues wrote in American Journal of Hematology.

Chemoimmunotherapy and single-agent ibrutinib are both acceptable first-line treatments of patients with CLL. However, outcomes of these two approaches have not been compared directly.

Ibrutinib was approved based on results from RESONATE-2, a phase III study that showed ibrutinib significantly prolonged progression-free survival (PFS) compared with chlorambucil, with an 84% reduced risk for progression or death, and longer overall survival (OS). Several trials of chemoimmunotherapy have shown benefit in patients with CLL, but there are concerns about toxicities, including infections and myelosuppression.

Here, the researchers compared results from RESONATE-2 with those of three phase III studies of chemoimmunotherapy in first-line treatment of CLL. Patients in those studies were treated with fludarabine/cyclophosphamide/rituximab (CLL8, CLL10), bendamustine/rituximab (CLL10), obinutuzumab/chlorambucil and rituximab/chlorambucil (CLL11), and ofatumumab/chlorambucil (COMPLEMENT-1).

The median age of patients included in these studies ranged from 61–74 years old. Older patients were enrolled in the ibrutinib studies and those of chlorambucil-based chemoimmunotherapy.

The median follow-up varied across studies ranging from 14.5–37.4 months. Among all included patients, the median PFS appeared longer with ibrutinib compared with chemoimmunotherapy; however, OS outcomes were comparable.

According to the researchers, the chemoimmunotherapy studies tended to exclude patients with 17p deletion or enrolled older/less-fit patients. Compared with these studies, PFS appeared favorable for ibrutinib in high-risk subgroups such as those with advanced disease or bulky lymph nodes. Additionally, ibrutinib appeared to have more favorable OS in older or less fit patients compared with chlorambucil-based chemoimmunotherapy including ofatumumab, rituximab, or obinutuzumab.

The researchers noted however, “that some patients benefit remarkably from first-line treatment with fludarabine, cyclophosphamide, and rituximab. According to an updated survival analysis from the CLL8 study, with a median follow up of 5.9 years, median PFS was 56.8 months and median OS was not reached following treatment with fludarabine-cyclophosphamide-rituximab.”

“Ongoing randomized studies in first-line CLL are currently evaluating ibrutinib alone or in combination with rituximab vs bendamustine and rituximab or fludarabine, cyclophosphamide, and rituximab, and ibrutinib plus obinutuzumab vs chlorambucil plus obinutuzumab,” the researchers detailed. “These studies will help further explore and confirm the role of ibrutinib as a first-line treatment for CLL."