At the ASH 2018 Annual Meeting, researchers reported up to 7 years of follow-up data for patients receiving single-agent ibrutinib in the first-line and relapsed/refractory (R/R) settings.
Of the 132 patients followed in the PCYC-1103 extension study, 31 received first-line ibrutinib and 101 had R/R disease. As of the latest data cutoff, 17 (55%) first-line and 21 (21%) R/R patients have continued ibrutinib treatment, with median follow-up of 67 months. Median age for all patients was 71 (first line) and 64 (R/R) years and 57% of patients were younger than 70 years of age (first line, 74%; R/R, 34%). More than one-half of patients have unmutated IGHV (first line, 48%; R/R, 78%).
With up to 7 years of follow-up, sustained activity of single-agent ibrutinib was seen in both first-line and R/R patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma, including those with high-risk genomic factors. In the analysis, the overall response rate was 89% for all patients, with similar rates in first-line (87% [complete response (CR), 32%]) and R/R (89% [CR, 10%]) patients. Median progression-free survival (PFS) was not reached for first-line patients and was 51 months for R/R patients. Estimated 6-year PFS rates were 88% and 37%, respectively. Median overall survival (OS) was not reached in either first-line or R/R patients, and estimated 6-year OS rates were 88% and 58%, respectively. Median PFS and 6-year PFS estimates were impressive in R/R patients with high-risk characteristics:
Grade ≥3 adverse events (AEs) were reported in fewer first-line (74%) patients than R/R (89%) patients, despite longer median time on treatment for first-line patients (72 months vs 39 months). Grade ≥3 AEs occurring more frequently among first-line patients included hypertension (32%), diarrhea (16%), and hyponatremia (10%); grade ≥3 AEs occurring more frequently among R/R patients were pneumonia (27%), neutropenia (21%), thrombocytopenia (11%), and cellulitis (9%). Grade ≥3 infections occurred in 23% of first-line patients and in 55% of R/R patients. Fatal AEs occurred in 6% of first-line and 17% of R/R patients. Overall, the number of serious AEs decreased over time.
Overall, ibrutinib responses were durable, with sustained PFS and OS rates in both first-line and R/R patients. In R/R CLL, ibrutinib administration in earlier lines of therapy resulted in improved PFS outcomes. Tolerability was similar to previous reports, and most grade ≥3 AEs declined over time.
Byrd JC, et al. ASH 2018. Abstract 3133.