Findings from the longest follow-up to date evaluating up to 5 years of ibrutinib (Imbruvica) in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) show that the agent is safe and effective.
Susan M. O'Brien, MD
Findings from the longest follow-up to date evaluating up to 5 years of ibrutinib (Imbruvica) in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) show that the agent is safe and effective, with 89% of both treatment-naïve (TN) and relapsed patients experiencing a complete or partial response to the therapy.
"These 5-year results suggest that both previously treated or untreated CLL/SLL patients may achieve robust and long-lasting responses with single-agent ibrutinib, with more patients developing a complete response over time," said lead investigator Susan O'Brien, MD.
O’Brien, associate director for clinical science at the Chao Family Comprehensive Cancer Center, University of California Irvine Health, presented the findings at the 2016 ASH Annual Meeting.
Additionally, patients lived without disease progression longer when ibrutinib is administered earlier than in the third line or beyond. "Our data suggest that starting treatment with ibrutinib as early as possible in CLL/SLL has promising clinical potential for long-term progression-free and overall survival," O’Brien said.
The follow-up data O’Brien presented at ASH are from the phase Ib/II PCYC-1102 trial, evaluating the safety and efficacy of single-agent ibrutinib in TN patients with CLL/SLLand relapsed/refractory (R/R) patients.
In her presentation, O’Brien reported long-term findings from this study based on 132 patients with CLL/SLL: 31 were TN and 101 patients R/R. Patients received either 420 mg or 840 mg once daily until disease progression or unacceptable toxicity. Among R/R patients, 34% haddel17p, 35% haddel11q, 47% haddel13qmutations, and 78% had unmutated IGVH.
The median age of study participants is 68 (range, 37-84 years), and 43% of the patients are aged ≥70. For all treated patients, the median time on study is 46 months; for untreated patients, it is 60 months; and for R/R patients (who had a median of 4 prior therapies), 39 months.
The primary endpoint is overall response rate (ORR). Secondary endpoints include duration of response, progression-free survival (PFS), and safety. The long-term data show that responses to ibrutinib are durable, reported O’Brien, with an ORR, according to investigator review, of 86%, and this included a complete response (CR) rate of 14% for all treated patients. In the TN group, ORR is 84%, and among R/R patients it is 86%.
Median duration of response has not been reached for TN patients and is 45 months for R/R patients. “Ninety-two percent of treatment-naïve patients are progression-free at 5 years,” O’Brien stated, adding that CR rates have increased over time to 29% for TN patients and to 10% in the R/R group. Median PFS has not been reached in the TN group; for R/R patients, median PFS is 52 months. The researchers estimate a 60-month PFS rate of 92% in the TN population and 43% in the R/R group.
O’Brien also commented on findings for higher-risk groups, and overall, patients without complex karyotype (CK) experienced more favorable PFS and OS than those with CK. “Survival outcomes for patients with complex karyotype ofdel17pwere less robust compared to those in lower-risk genetic groups,” O’Brien noted. “Additionally, in a multivariate analysis,del17pis identified as a significant predictor of PFS and overall survival.”
A long-term extension study (PCYC-1103), collected data on grade ≥3 adverse events (AEs), serious AEs, and AEs requiring dose reduction or discontinuation.
“Ibrutinib is well-tolerated,” O’Brien said, “with onset of most new grade ≥3 AEs decreasing over time.” Among all patients, the onset of most grade 3 or higher treatment-emergent AEs was highest in the first year and decreased over time. Twenty-seven patients (20%) stopped treatment due to AEs, and 34 patients due to disease progression.
With approximately 5 years of follow-up, the most frequent grade 3 or higher AEs were hypertension (26%), pneumonia (22%), neutropenia (17%), thrombocytopenia (9%), and atrial fibrillation (9%).
“Ibrutinib’s manageable safety profile allows for extended dosing,” O’Brien concluded. “Sixty-five percent of older TN patients and 30% of R/R patients continue treatment with 5 years of follow-up.”