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

Jan A. Burger, Tadeusz Robak, Fatih Demirkan, Osnat Bairey, Carol Moreno, David Simpson, Talha Munir, Don A. Stevens, Sandra Dai, Leo W.K. Cheung, Kevin Kwei, Indu Lal, Emily Hsu, Thomas J. Kipps, Alessandra Tedeschi

Research output: Contribution to journalArticlepeer-review

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).

Original languageEnglish
Pages (from-to)1375-1386
Number of pages12
JournalLeukemia and Lymphoma
Volume63
Issue number6
DOIs
StatePublished - 2022
Externally publishedYes

Keywords

  • chlorambucil
  • Chronic lymphocytic leukemia
  • ibrutinib
  • obinutuzumab
  • pooled analysis

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