Up to 6.5 years (median 4 years) of follow-up of first-line ibrutinib in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma and high-risk genomic features: integrated analysis of two phase 3 studies

Burger J. A., Robak T., DEMİRKAN F., Bairey O., Moreno C., Simpson D., ...More

LEUKEMIA & LYMPHOMA, vol.63, no.6, pp.1375-1386, 2022 (SCI-Expanded, Scopus) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 63 Issue: 6
  • Publication Date: 2022
  • Doi Number: 10.1080/10428194.2021.2020779
  • Journal Name: LEUKEMIA & LYMPHOMA
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.1375-1386
  • Keywords: Chronic lymphocytic leukemia, ibrutinib, chlorambucil, obinutuzumab, pooled analysis
  • Dokuz Eylül University Affiliated: Yes

Abstract

Genomic abnormalities, including del(17p)/TP53 mutation, del(11q), unmutated IGHV, and mutations in BIRC3, NOTCH1, SF3B1, and XPO1 predict poor outcomes with chemoimmunotherapy in chronic lymphocytic leukemia. To better understand the impact of these high-risk genomic features on outcomes with first-line ibrutinib-based therapy, we performed pooled analysis of two phase 3 studies with 498 patients randomized to receive ibrutinib- or chlorambucil-based therapy with median follow-up of 49.1 months. Ibrutinib-based therapy improved overall response rates (ORRs), complete response rates, and progression-free survival (PFS) versus chlorambucil-based therapy across all subgroups. In ibrutinib-randomized patients with versus without specified genomic features, ORR and PFS were comparable across subgroups. PFS hazard ratio (95% CI) for del(17p)/TP53 mutated/BIRC3 mutated: 1.05 (0.54-2.04); del(17p)/TP53 mutation, del(11q), and/or unmutated IGHV: 1.11 (0.69-1.77); unmutated IGHV: 1.79 (0.99-3.24); and NOTCH1 mutated 1.05 (0.65-1.69). This integrated analysis demonstrated efficacy of first-line ibrutinib-based treatment irrespective of cytogenetic and mutational risk features. Registered at ClinicalTrials.gov (NCT01722487 and NCT02264574).