John Byrd, MD
Single-agent ibrutinib continued to demonstrate strong results after 7 years of follow-up in both the frontline and heavily pretreated, relapsed/refractory setting for patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), according to findings from a phase Ib/II trial and an extension study presented at the 2018 ASH Annual Meeting.
In the frontline setting, the median progression-free survival (PFS) and median overall survival (OS) were still not yet met. The 7-year PFS rate in this setting was 80% and the OS rate was 75%. In the relapsed/refractory setting, the 7-year PFS rate was 32% and the OS rate was 52%. The median PFS in this group was 51 months and the median OS was not yet reached.
“The long-term follow-up data with ibrutinib continues to look promising, with remissions that suggest patients are able to live many years beyond what was previously expected,” lead investigator John C. Byrd, MD, Warren Brown Chair of Leukemia Research, Professor of Medicine at the Ohio State University, said in a statement. “These data also suggest that starting treatment with ibrutinib as early as possible for CLL and SLL provides the best efficacy over the long-term – an important factor that treating physicians should consider.”
Between the phase Ib/II and extension study, 132 patients with CLL and SLL were treated with single-agent ibrutinib. Of these patients, 31 were treatment-naive and 101 had relapsed/refractory disease. Patients received either 420 mg or 840 mg once daily of ibrutinib. Among the relapsed/refractory patients, 34% had del17p, 35% had del11q, 47% had del13q mutations, and 78% had unmutated IGVH. The median age of study participants is 68 (range, 37-84 years), and 43% of the patients were 70 or older.
The objective response rate (ORR) was 89% across the full study, which included a complete remission (CR) rate of 15%. In those with previously untreated disease, the ORR was 87% and for those with relapsed/refractory disease the ORR was 89%. The CR rates were 32% in the untreated group and 10% in the pretreated population. The median duration of response was not reached in the newly-diagnosed cohort and was 57 months in relapsed/refractory patients.
Overall, there were no new or unexpected adverse events (AEs) seen with longer follow up. Grade 3/4 AEs were reported in 74% of newly diagnosed patients and for 89% of those with relapsed/refractory disease, with serious AEs seen in 61% and 76% of patients in these groups, respectively. The most common grade ≥3 treatment-emergent AEs were hypertension (newly diagnosed, 32%; relapse/refractory, 26%), diarrhea (newly diagnosed, 16%; relapse/refractory, 4%), and hyponatremia (newly diagnosed, 10%; relapse/refractory, 0%).
Across both patient groups, 11% of patients experienced a major hemorrhage or grade ≥3 atrial fibrillation, thrombocytopenia, anemia, and arthralgia. Additionally, infections were seen in 23% of those with newly diagnosed disease and for 55% of those with relapsed/refractory disease.
“With up to 7 years of follow up, Imbruvica monotherapy continues to show long-lasting responses and survival benefits in patients with CLL and SLL,” Danelle James, MD, MAS, head of Clinical Science, Pharmacyclics LLC, an AbbVie company, said in a press release. “These results help demonstrate that the benefits of Imbruvica can be sustained for many years, which were seen in patients with CLL and SLL that are typically more difficult to treat due to high-risk genomic factors.”
Ibrutinib was initially approved by the FDA in 2013 for the treatment of patients with mantle cell lymphoma. The agent is currently approved at 420 mg once daily for the treatment of CLL/SLL and Waldenstrom macroglobulinemia. In addition to these indications, ibrutinib is also approved at 560 mg per day for marginal zone lymphoma.
Byrd JC, Furman RR, Coutre S, et al. Up to 7 Years of Follow-up of Single-Agent Ibrutinib in the Phase 1b/2 PCYC-1102 Trial of First Line and Relapsed/Refractory Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Presented at: 2017 ASH Annual Meeting; December 9-12, 2017. Abstract 3133.
<<< 2018 ASH Annual Meeting