Phase 3 RESONATE-2 Data Yield First-Line Approval for Ibrutinib in CLL

Just 2 days after being rejected by cost regulators in the UK, ibrutinib (Imbruvica) has been approved for the frontline treatment of patients with chronic lymphocytic leukemia in the United States. Results from a randomized, multi-center, open-label phase 3 trial (RESONATE-2) convinced the FDA that the drug can improve outcomes for patients with chronic lymphocytic leukemia (CLL) compared with chlorambucil, the current standard of care in patients who cannot tolerate strong chemotherapy.

“This approval represents a significant leap forward for patients diagnosed with CLL who may want to consider an alternative first-line treatment to traditional chemotherapy,” said Michael Severino, MD, executive vice president, research and development and chief scientific officer, AbbVie, in a statement.

Trial results were released at the 2015 annual meeting of the American Society of Hematology and simultaneously published in The New England Journal of Medicine. The trial evaluated progression-free survival (PFS) in 269 treatment-naïve patients, 65 years of age or older, who were diagnosed with CLL or small lymphocytic lymphoma and were treated with ibrutinib or chlorambucil. At 18.4 months, the median PFS for ibrutinib was not reached, while the median PFS for chlroambucil was attained at 18.9 months. Additionally, the study found that ibrutinib reduced the risk of death or disease progression by 84% compared with chlorambucil (hazard ratio, 0.16; P<.001). The overall response rate of ibrutinib (86%) was also significantly (P<.001) greater than that of chlorambucil (35%), the study reported.

The National Comprehensive Cancer Network recently updated its Guidelines to grant ibrutinib a category 1 recommendation for those patients with CLL who are frail and suffer significant comorbidities, patients with or without del 17p or the genetic mutation TP53 who are 70 years or older, or younger patients with significant comorbidities.

The lead investigator of the study Jan Burger, MD, PhD, associate professor, MD Anderson Cancer Center, said, “The progression-free survival data seen in these previously untreated CLL patients are strong and encouraging. This is especially important for first-line CLL patients, when considering the safety profile. This treatment represents another option for these patients.”

The adverse event warnings for ibrutinib include hemorrhage, infections, cytopenias, atrial fibrillation, hypertension, second primary malignancies, embryo-fetal toxicity, and tumor lysis syndrome. The most commonly occurring adverse reactions of all grades in CLL patients treated with ibrutinib in the RESONATE-2 trial were diarrhea, musculoskeletal pain, cough, and rash.

Cost?

A study published last year in the Journal of Oncology Practice claimed that ibrutinib would have a substantial impact on the cumulative cost of CLL care in the United States, especially considering that the drug would need continuous daily use. With an average wholesale price estimated at $118,000 annually, they estimated that the total out-of-pocket cost for 100 patients with newly diagnosed CLL under Medicare Part D would be about $1,031,367 ($35,564 for every treated patient). These high costs could potentially undermine the promise of this agent due to access and adherence issues, the authors concluded in their study.

Reference

1. Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015; 373:2425-2437.

2. Shanafelt TD, Borah BJ, Finnes HD, et al. Impact of ibrutinib and idelalisib on the pharmaceutical cost of treating chronic lymphocytic leukemia at the individual and societal levels. JOP. 2015; 11(3):252-258.