PFS and ORR benefits of first-line ibrutinib-based treatment in CLL

An integrated analysis of the two phase 3 studies RESONATE-2 and iLLUMINATE with up to 6.5 years follow-up confirmed significant benefits in progression-free survival (PFS) and overall response rate (ORR) with first-line ibrutinib with or without obinutuzumab versus chlorambucil-based therapy. Similar PFS and ORR was demonstrated for ibrutinib-treated patients with or without high-risk genomic features [1].

Genomic abnormalities, such as mutations in TP53, BIRC3, NOTCH1, del(11q), and unmutated IGHV are risk factors that predict inferior outcomes with chemoimmunotherapy in patients with chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) [2]. Ibrutinib is the only once-daily Bruton’s tyrosine kinase (BTK) inhibitor showing a significant benefit in PFS and overall survival (OS) compared with established therapies in patients with previously untreated or relapsed/refractory CLL/SLL [3-5]. To better understand outcomes in patients with treatment-naïve CLL with various high-risk genomic features, Prof. Jan Burger (MD Anderson Cancer Center, Texas, USA) and colleagues performed a pooled analysis of two phase 3 studies.

In RESONATE-2 (NCT01722487), patients aged ≥65 years without TP53 mutation were randomised to single-agent ibrutinib or chlorambucil [3,4]. In iLLUMINATE (NCT02264574), patients aged ≥65 years, or <65 years with coexisting conditions or TP53 mutation, were randomised to ibrutinib-obinutuzumab or chlorambucil-obinutuzumab [5].

Ibrutinib-based therapy significantly improved ORR and PFS compared with chlorambucil-based therapy [1]. At 42 months, PFS rates were significantly higher across high-risk genomic subgroups in ibrutinib-treated patients (63-82%) compared with chlorambucil-treated patients (6-34%). Consistent PFS benefits with ibrutinib were observed across all high-risk genomic subgroups.

1. Burger JA, et al. Outcomes of First-Line Ibrutinib in Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) and High-Risk Genomic Features with up to 6.5 Years Follow-up: Integrated Analysis of Two Phase 3 Studies (RESONATE-2 and iLLUMINATE). 62^nd ASH Annual Meeting, 5-8 December 2020. Abstract 2220.
2. Byrd JC, et al. J Clin Oncol. 2006 Jan 20;24:437-43.
3. Burger JA, et al. Leukemia. 2020;34:787-98.
4. Byrd JC, et al. Blood. 2019;133:2031-42.
5. Moreno C, et al. Lancet Oncol. 2019;20:43-56.

Posted on 18 February 202122 February 2021