The safety and efficacy of Ibrutinib ( Imbruvica ), a once-daily Bruton's tyrosine kinase inhibitor, in chronic lymphocytic leukemia / small lymphocytic lymphoma ( CLL/SLL ) was demonstrated in this phase 1b/2 study.
Extended follow-up up to 8 years is described, representing the longest follow-up for single-agent Ibrutinib, or any BTK inhibitor, to date.
Phase 1b/2 PCYC-1102 and extension study PCYC-1103 included patients receiving single-agent Ibrutinib in first-line or relapsed / refractory CLL/SLL.
Overall response rate was 89%, with similar rates in first-line ( 87%; complete response, 35% ) and relapsed / refractory settings ( 89%; 10% ).
Estimated 7-year progression-free survival ( PFS ) rates were 83% in first-line and 34% in relapsed / refractory settings.
Forty-one patients had CLL progression ( n=11 with Richter's transformation ).
Median PFS was not reached with first-line Ibrutinib.
In relapsed/refractory CLL/SLL, median PFS was 52 months overall, 26 months in patients with chromosome 17p deletion, 51 months with 11q deletion, not reached with trisomy 12 or 13q deletion, and 88 months in patients without these cytogenetic abnormalities.
Estimated 7-year overall survival rates were 84% in first-line and 55% in relapsed / refractory settings.
Grade 3 or more adverse events in 15% or more of patients were hypertension ( 28% ), pneumonia ( 24% ), and neutropenia ( 18% ).
These grade greater than or equal to 3 adverse effects generally declined over time, except hypertension.
Adverse reactions leading to discontinuation in 2 or more patients were only observed in the relapsed / refractory setting ( sepsis, diarrhea, subdural hematoma, Richter's transformation ).
In conclusion, with up to 8 years of follow-up, sustained responses and long-term tolerability of single-agent Ibrutinib were observed with treatment of first-line or relapsed / refractory CLL/SLL, including high-risk CLL/SLL. ( Xagena )
Byrd JC et al, Clin Cancer Res 2020; Online ahead of print