Long-term efficacy of first-line ibrutinib treatment for chronic lymphocytic leukaemia in patients with TP53 aberrations: a pooled analysis from four clinical trials


Por: Allan, JN, Shanafelt, T, Wiestner, A, Moreno, C, O'Brien, SM, Li, JL, Krigsfeld, G, Dean, JP, Ahn, IE

Publicada: 1 feb 2022 Ahead of Print: 1 dic 2021
Resumen:
TP53 aberrations [del(17p) or TP53 mutation] predict poor survival with chemoimmunotherapy in patients with chronic lymphocytic leukaemia (CLL). We evaluated long-term efficacy and safety of first-line ibrutinib-based therapy in patients with CLL bearing TP53 aberrations in a pooled analysis across four studies: PCYC-1122e, RESONATE-2 (PCYC-1115/16), iLLUMINATE (PCYC-1130) and ECOG-ACRIN E1912. The pooled analysis included 89 patients with TP53 aberrations receiving first-line treatment with single-agent ibrutinib (n = 45) or ibrutinib in combination with an anti-CD20 antibody (n = 44). All 89 patients had del(17p) (53% of 89 patients) and/or TP53 mutation (91% of 58 patients with TP53 sequencing results available). With a median follow-up of 49 center dot 8 months (range, 0 center dot 1-95 center dot 9), median progression-free survival was not reached. Progression-free survival rate and overall survival rate estimates at four years were 79% and 88%, respectively. Overall response rate was 93%, including complete response in 39% of patients. No new safety signals were identified in this analysis. Forty-six percent of patients remained on ibrutinib treatment at last follow-up. With median follow-up of four years (up to eight years), results from this large, pooled, multi-study data set suggest promising long-term outcomes of first-line ibrutinib-based therapy in patients with TP53 aberrations. Registered at ClinicalTrials.gov (NCT01500733, NCT01722487, NCT02264574 and NCT02048813).

Filiaciones:
Allan, JN:
 Weill Cornell Med, 407 E 61st St, New York, NY 10065 USA

Shanafelt, T:
 Stanford Univ, Med Ctr, Stanford, CA 94305 USA

Wiestner, A:
 NHLBI, Bldg 10, Bethesda, MD 20892 USA

Moreno, C:
 Autonomous Univ Barcelona, Hosp Santa Creu & St Pau, Barcelona, Spain

O'Brien, SM:
 Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Irvine, CA USA

Li, JL:
 AbbVie Co, Pharmacycl LLC, Sunnyvale, CA USA

Krigsfeld, G:
 AbbVie Co, Pharmacycl LLC, Sunnyvale, CA USA

Dean, JP:
 AbbVie Co, Pharmacycl LLC, Sunnyvale, CA USA

Ahn, IE:
 NHLBI, Bldg 10, Bethesda, MD 20892 USA
ISSN: 00071048
Editorial
WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, Reino Unido
Tipo de documento: Article
Volumen: 196 Número: 4
Páginas: 947-953
WOS Id: 000726330000001
ID de PubMed: 34865212
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