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
Por:
Burger, JA, Robak, T, Demirkan, F, Bairey, O, Moreno, C, Simpson, D, Munir, T, Stevens, DA, Dai, S, Cheung, LWK, Kwei, K, Lal, I, Hsu, EM, Kipps, TJ, Tedeschi, A
Publicada:
12 may 2022
Ahead of Print:
1 ene 2022
Resumen:
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).
Filiaciones:
Burger, JA:
Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA
Robak, T:
Med Univ Lodz, Copernicus Mem Hosp, Lodz, Poland
Demirkan, F:
Dokuz Eylul Univ, Izmir, Turkey
Bairey, O:
Rabin Med Ctr, Petah Tiqwa, Israel
Moreno, C:
Autonomous Univ Barcelona, Hosp Santa Creu & St Pau, Barcelona, Spain
Simpson, D:
BeiGene, San Mateo, CA USA
Munir, T:
St James Hosp, Dept Haematol, Leeds, W Yorkshire, England
Stevens, DA:
Norton Canc Inst, Louisville, KY USA
Dai, S:
Pharmacyclics LLC, San Francisco, CA USA
Cheung, LWK:
Pharmacyclics LLC, San Francisco, CA USA
Kwei, K:
Pharmacyclics LLC, San Francisco, CA USA
Lal, I:
Pharmacyclics LLC, San Francisco, CA USA
Hsu, EM:
Pharmacyclics LLC, San Francisco, CA USA
Kipps, TJ:
Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA
Tedeschi, A:
ASST Grande Osped Metropolitano Niguarda, Milan, Italy
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