RESONATE-2 is a phase 3 study of first-line Ibrutinib ( Imbruvica ) versus Chlorambucil in chronic lymphocytic leukemia ( CLL ) / small lymphocytic lymphoma ( SLL ).
Patients aged greater than or equal to 65 years ( n = 269 ) were randomized 1:1 to once-daily Ibrutinib 420 mg continuously or Chlorambucil 0.5-0.8 mg/kg for less than or equal to 12 cycles.
With a median ( range ) follow-up of 60 months ( 0.1-66 ), progression-free survival ( PFS ) and overall survival ( OS ) benefits for Ibrutinib versus Chlorambucil were sustained ( PFS estimates at 5 years: 70% vs 12%; hazard ratio, HR [ 95% CI ]: 0.146 [ 0.098-0.218 ]; OS estimates at 5 years: 83% vs 68%; HR [ 95% CI ]: 0.450 [ 0.266-0.761 ] ).
Ibrutinib benefit was also consistent in patients with high prognostic risk ( TP53 mutation, 11q deletion, and/or unmutated IGHV ) ( PFS: HR [ 95% CI ]: 0.083 [ 0.047-0.145 ]; OS: HR [ 95% CI ]: 0.366 [ 0.181-0.736 ] ).
Investigator-assessed overall response rate was 92% with Ibrutinib ( complete response, 30%; 11% at primary analysis ).
Common grade greater than or equal to 3 adverse events included neutropenia ( 13% ), pneumonia ( 12% ), hypertension ( 8% ), anemia ( 7% ), and hyponatremia ( 6% ); occurrence of most events as well as discontinuations due to adverse effects decreased over time.
Fifty-eight percent of patients continue to receive Ibrutinib. Single-agent Ibrutinib demonstrated sustained PFS and OS benefit versus Chlorambucil and increased depth of response over time. ( Xagena )
Burger JA et al, Leukemia 2019; Epub ahead of print