Paul Barr, MD
At 29 months’ follow-up, frontline ibrutinib (Imbruvica) reduced the risk of progression or death by 88% versus chlorambucil in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to the latest findings from the phase III RESONATE-2 trial presented at the 2016 ASH Annual Meeting.
The 24-month progression-free survival (PFS) rate was 89% in the ibrutinib arm compared with 34% in the chlorambucil arm (HR, 0.121; 95% CI 0.074-0.198; P
<.0001). PFS was significantly improved for ibrutinib across high-risk subgroups, including del11q and the unmutated IGHV gene, according to lead study author Paul Barr, MD, assistant professor of Medicine, University of Rochester, Wilmot Cancer Institute.
“Ibrutinib continues to demonstrate overall (OS) benefit over chlorambucil,” added Bar. The 24-month OS was 95% in the ibrutinib arm compared with 84% in the chlorambucil arm. “Complete response (CR) to ibrutinib continues to improve over time, increasing from 7% at 12 months to 15% at 24 months. At a median follow-up of 29 months, the CR rate is at 18%,” said Barr.
In RESONATE-2, 269 treatment-naïve patients diagnosed with CLL/SLL, who were at least 65 years old, were randomized 1:1 to either chlorambucil or ibrutinib. Patients with a 17p deletion were excluded from the study. Patients received 420 mg of ibrutinib once daily until progression or chlorambucil at 0.5 mg/kg on days 1 and 15 of a 28-day cycle, for up to 12 cycles. Patients continued on the study until study closure or disease progression. “Fifty-five patients on the chlorambucil arm crossed over to the ibrutinib arm due to disease progression,” Barr said.
The primary trial endpoint was PFS. Secondary endpoints included OS, objective response rate, rate of hematologic improvement, and safety.
Sustained improvements in hematological functions of patients were observed and were higher for ibrutinib compared with chlorambucil. In patients with anemia, hemoglobin levels were 90% versus 45% (P
<.0001) with ibrutinib versus chlorambucil, respectively. In patients with thrombocytopenia, platelet counts were at 80% versus 46% (P
= .0055), respectively.
“Ibrutinib is a good option because most patients remain on ibrutinib therapy at 29 months,” Barr said. He showed that 79% of patients have remained on ibrutinib, and 83% of participants continued on treatment for at least 2 years. Of the 21% patients who discontinued the drug, 3% had disease progression, 12% had adverse events (AEs), 4% died, and 1% withdrew consent.
In terms of AEs, atrial fibrillation was slightly higher (10%) than in other studies of ibrutinib, which could be because of the higher average age of this cohort, Barr explained. Of the 16 patients who discontinued ibrutinib treatment due to AEs, 13 remained alive after 13 months of follow-up. Some of the other AEs observed in the ibrutinib arm included major hemorrhage, diarrhea, and anemia.
“The quality of responses in patients with CLL/SLL being treated with single-agent ibrutinib continues to improve with time,” Barr concluded. “Further, rates of treatment-limiting AEs decreased over time, and a majority of the elderly patient population in the trial remains on daily ibrutinib,” said Barr.
This article was repurposed from AJMC.com
Barr PM, Robak T, Owen CJ, et al. Updated efficacy and safety from the phase 3 RESONATE-2 study: ibrutinib as firstline treatment option in patients 65 years and older with chronic lymphocytic leukemia/small lymphocytic leukemia. Presented at: 58th American Society of Hematology Annual Meeting & Exposition; December 3, 2016; San Diego, CA. Abstract 234.