CHICAGO—In patients with pretreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), adding ibrutinib to the standard combination of bendamustine and rituximab (BR) significantly reduced the risk of disease progression versus BR + placebo – to the tune of 80 percent – according to interim results from the phase III HELIOS study.
The results were presented by Asher Alban Chanan-Khan, MD, professor of Medicine at Mayo Clinic in Jacksonville, Florida, in a late-breaking abstract at the 2015 ASCO Annual Meeting.
Calling the results a “blessing for patients,” Dr. Chanan-Khan said, “This finding represents a significant advancement in the management and treatment of this leukemia. Although CLL remains incurable, this new regimen offers longer disease control and a decreased risk of relapse for our patients.”
In the double-blind phase III HELIOS trial, Dr. Chanan-Khan and investigators randomized 578 previously treated patients with relapsed/refractory CLL or SLL to either BR plus placebo (n=289) or BR plus ibrutinib (420 mg/day; n=289). Patients had received an average of two prior therapies at time of enrollment, and 38 percent of the population had Rai stage III/IV disease.
Patients were set to receive a maximum of six treatment cycles; 83 percent and 78 percent of patients completed the full six cycles of ibrutinib + BR and placebo + BR, respectively.
The rate of PFS (the study’s primary endpoint) was significantly increased with the ibrutinib plus BR combination: PFS was not reached in the ibrutinib arm, but was 13.3 months in the placebo arm (HR=0.02; 95% CI 0.15-0.27). This translated to an 80 percent reduction in the risk for progression or death with ibrutinib.
Ibrutinib treatment also improved overall response rates (ORR) and complete response rates (CRR) compared with placebo (82.7% vs. 67.8% [p<0.0001] for ORR and 10.4% vs. 2.8% for CRR). Analysis for overall survival also showed a non-significant 37 percent reduction in the risk of death with ibrutinib, though the finding was non-significant (p=0.0598).
The toxicity profiles were similar between both treatment arms, with neutropenia (58.2% for ibrutinib vs. 54.7% for placebo) and nausea (36.9% vs. 35.2%) as the most common all-grade adverse events.
Due to the promising results seen in the interim analysis in March 2015, 90 patients in the placebo arm were allowed to cross over to the ibrutinib arm.
Commenting on the interim results in a press release, HELIOS study investigator Simon Rule, MD, of Derriford Hospital in Plymouth, United Kingdom echoed Dr. Chanan-Khan’s sentiments: “We knew ibrutinib was an effective single-agent treatment option with an established safety profile and we now have additional evidence suggesting that ibrutinib improves outcomes when combined with existing treatment regimens. [These results] are very encouraging for previously-treated patients with CLL or SLL and suggest that the ibrutinib combination may be an option for these patients moving forward.”
Source: Chanan-Khan AAA, Cramer P, Demirkan F, et al. Ibrutinib combined with bendamustine and rituximab (BR) in previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma. Abstract #LBA7005. Presented at the 2015 American Society of Clinical Oncology Annual Meeting, Chicago, IL, May 30, 2015.