Impact of Minimal Residual Disease on Progression-Free Survival Outcomes after Fixed-Duration Ibrutinib-Venetoclax Versus Chlorambucil-Obinutuzumab in the GLOW Study
Munir, Talha (St James's Hospital)
Moreno, Carol (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Owen, Carolyn (Tom Baker Cancer Centre)
Follows, George (Addenbrookes Hospital (Cambridge, Regne Unit))
Benjamini, Ohad (Sheba Medical Center)
Janssens, Ann (UZ Leuven Gasthuisberg)
Levin, Mark-David (Albert Schweitzer Hospital)
Osterborg, Anders (Karolinska University Hospital and Karolinska Institutet (Suecia))
Robak, Tadeusz (Medical University of Lodz. Copernicus Memorial Hospital)
Simkovic, Martin (University Hospital Hradec Kralove (República Txeca))
Stevens, Don (Norton Cancer Institute)
Voloshin, Sergey (Russian Scientific and Research Institute of Hematology and Transfusiology)
Vorobyev, Vladimir (S.P. Botkin Moscow City Clinical Hospital)
Yagci, Munci (Gazi Universitesi Tip Fakultesi)
Ysebaert, Loic (Institut Universitaire du Cancer Toulouse Oncopole)
Qi, Keqin (Janssen Research & Development)
Qi, Qianya (Janssen Research & Development)
Parisi, Lori (Janssen Research & Development)
Srinivasan, Srinivasan (Oncology Translational Research. Janssen Research & Development)
Schuier, Natasha (Janssen Research & Development)
Baeten, Kurt (Janssen Research & Development)
Howes, Angela (Janssen Research & Development)
Caces, Donne Bennett (Janssen Research & Development)
Niemann, Carsten U (Rigshospitalet Copenhagen University Hospital)
Kater, Arnon P. (Amsterdam Medical Centers. University of Amsterdam)

Data:	2023
Resum:	PURPOSEIn GLOW, fixed-duration ibrutinib + venetoclax showed superior progression-free survival (PFS) versus chlorambucil + obinutuzumab in older/comorbid patients with previously untreated chronic lymphocytic leukemia (CLL). The current analysis describes minimal residual disease (MRD) kinetics and any potential predictive value for PFS, as it has not yet been evaluated for ibrutinib + venetoclax treatment. METHODSUndetectable MRD (uMRD) was assessed by next-generation sequencing at <1 CLL cell per 10,000 (<10-4) and <1 CLL cell per 100,000 (<10-5) leukocytes. PFS was analyzed by MRD status at 3 months after treatment (EOT+3). RESULTSIbrutinib + venetoclax achieved deeper uMRD (<10-5) rates in bone marrow (BM) and peripheral blood (PB), respectively, in 40. 6% and 43. 4% of patients at EOT+3 versus 7. 6% and 18. 1% of patients receiving chlorambucil + obinutuzumab. Of these patients, uMRD (<10-5) in PB was sustained during the first year post-treatment (EOT+12) in 80. 4% of patients receiving ibrutinib + venetoclax and 26. 3% receiving chlorambucil + obinutuzumab. Patients with detectable MRD (dMRD; ≥10-4) in PB at EOT+3 were more likely to sustain MRD levels through EOT+12 with ibrutinib + venetoclax versus chlorambucil + obinutuzumab. PFS rates at EOT+12 were high among patients treated with ibrutinib + venetoclax regardless of MRD status at EOT+3: 96. 3% and 93. 3% in patients with uMRD (<10-4) and dMRD (≥10-4) in BM, respectively, versus 83. 3% and 58. 7% for patients receiving chlorambucil + obinutuzumab. PFS rates at EOT+12 also remained high in patients with unmutated immunoglobulin heavy-chain variable region (IGHV) receiving ibrutinib + venetoclax, independent of MRD status in BM. CONCLUSIONMolecular and clinical relapses were less frequent during the first year post-treatment with ibrutinib + venetoclax versus chlorambucil + obinutuzumab regardless of MRD status at EOT+3 and IGHV status. Even for patients not achieving uMRD (<10-4), PFS rates remained high with ibrutinib + venetoclax; this is a novel finding and requires additional follow-up to confirm its persistence over time.
Nota:	Supported by Janssen Research & Development, LLC.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Aged ; Antineoplastic Combined Chemotherapy Protocols ; Bridged Bicyclo Compounds, Heterocyclic ; Chlorambucil ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; Neoplasm, Residual ; Progression-Free Survival
Publicat a:	Journal of Clinical Oncology, Vol. 41 Núm. 21 (20 2023) , p. 3689-3699, ISSN 1527-7755

DOI: 10.1200/JCO.22.02283
PMID: 37279408

17 p, 1.2 MB

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