Single-Agent Ibrutinib Active at 5 Years in CLL, SLL

Treatment with single-agent ibrutinib resulted in sustained efficacy and durable responses in patients with treatment-naive or relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to recently published 5-year results.

“Our comprehensive 5-year experience with single-agent ibrutinib in patients with TN and R/R CLL demonstrates the sustained efficacy of long-term treatment with ibrutinib despite the presence of high-risk genomic features in a large proportion of our patient population,” Susan O’Brien, MD, of the University of Texas MD Anderson Cancer Center, and colleagues wrote in Blood. “Extended treatment with ibrutinib was well tolerated with no new safety signals, and the occurrence of severe AEs generally diminished over time with continued ibrutinib therapy.”

Results of their phase Ib/II study of single-agent ibrutinib in this patient population showed high overall response rates and sustained remission. Patients who continued on an extension study showed sustained activity of ibrutinib with manageable toxicity over a 3-year period. The overall response rate was 89%, with 11% of these patients achieving a complete response.

This updated analysis followed patients for a median of 5 years.

At 5 years, treatment with ibrutinib continued to result in an overall response rate of 89% with complete response rates increasing to 29% in patients with treatment-naive disease and 10% in patients with R/R disease.

Progression-free survival at 5 years was 92% for treatment-naive patients and 44% in R/R patients. The median progression-free survival was not yet reached for treatment-naive patients and was 51 months for those with R/R disease. In patients with high-risk genomic features like del(11q), del(17p), and unmutated IGHV, median progression-free survival was 51, 26, and 43 months, respectively.

In treatment-naive disease, patients were treated with ibrutinib for an average of 65 months, with the majority (77%) on treatment for more than 4 years. The most common adverse events leading to treatment discontinuation were one case each of fatigue, viral infection, malignant neoplasm, pruritic rash, skin lesion, and hypertension. At 5 years, more than half (55%) of patients remained on treatment.

Among patients with R/R disease, the median treatment duration was 39 months, with 39% of patients remaining on treatment for longer than 4 years. Seventy-two percent of patients discontinued treatment due to disease progression or adverse events. Events leading to discontinuation were sepsis, diarrhea, subdural hematoma, and atrial fibrillation. At 5 years, 28% of patients are still on treatment.