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We report long-term outcomes of ibrutinib-venetoclax in older\/comorbid patients at 67-month median follow-up of the phase III GLOW study (NCT03462719) and report grade 3\/4 treatment-emergent adverse event (TEAE)-free progression-free survival (PFS). Patients were randomized 1:1 to ibrutinib-venetoclax (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009106) or chlorambucil-obinutuzumab (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009105). Sixty-six-month overall survival (OS) rates were 79.0% and 60.8% for ibrutinib-venetoclax and chlorambucil-obinutuzumab, respectively (hazard ratio [HR] 0.46). Ibrutinib-venetoclax reduced the risk of requiring second-line therapy by 77.4% and continued to improve PFS vs chlorambucil-obinutuzumab (66-month rates: 51.7% vs 18.1%, HR 0.27), regardless of IGHV\/measurable residual disease (MRD) status. Ibrutinib-venetoclax-treated patients with undetectable MRD at end-of-treatment had better PFS outcomes than those with detectable MRD, especially in patients with unmutated IGHV. Grade 3\/4 TEAE-free PFS was 21.4 months longer for ibrutinib-venetoclax vs chlorambucil-obinutuzumab (51.6 vs 30.2 months). Ibrutinib-venetoclax maintains superior OS, superior PFS, reduction in need for second-line treatment, and longer PFS duration without grade 3\/4 TEAEs vs chlorambucil-obinutuzumab. Fixed-duration ibrutinib-venetoclax is an effective first-line treatment option for older\/comorbid patients with previously untreated CLL, providing durable disease control and preserving future treatment options.\n                  <\/jats:p>","DOI":"10.1038\/s41375-026-03150-7","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:03:51Z","timestamp":1790928231000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["First-line ibrutinib-venetoclax in chronic lymphocytic leukemia: GLOW 67-month results and grade 3\/4 adverse event-free progression-free survival"],"prefix":"10.1038","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9880-5242","authenticated-orcid":false,"given":"Carsten","family":"U. 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TM reports advisory boards for AbbVie, Alexion, AstraZeneca, Gilead, Johnson & Johnson, and Morphosys; and honoraria from AbbVie, Alexion, Apellis, AstraZeneca, Gilead, Johnson & Johnson, and Novartis. CO reports advisory boards, consultancy, and honoraria from AbbVie, AstraZeneca, BeiGene, Eli Lilly, Gilead, Incyte, Johnson & Johnson, Merck, Roche, Seattle Genetics, and Servier; and speaking engagements for AbbVie and AstraZeneca. GF reports consultancy for AbbVie, AstraZeneca, Eli Lilly, Johnson & Johnson, Roche, and Takeda. J-\u00c1H-R reports scientific talks for AbbVie, Amgen, AstraZeneca, BeiGene, BMS-Celgene, Gilead, Johnson & Johnson, Lilly, Roche, and Takeda; advisory boards for AbbVie, Amgen, AstraZeneca, BeiGene, BMS-Celgene, Gilead, Incyte, Johnson & Johnson, Jazz Pharmaceuticals, Lilly, MSD, Roche, Rovi, and Takeda; and grant\/research support from BMS (Celgene). OB reports no conflicts of interest. A.J. reports advisory boards, consultancy, and\/or speaker for AbbVie, Amgen, Argenx, AstraZeneca, BeiGene, Eli Lilly, Johnson & Johnson, MSD, Novartis, Sobi, and Takeda; and travel expenses from AbbVie and AstraZeneca. M-DL reports advisory board and travel expenses from AbbVie, Johnson & Johnson, and Roche. T.R. reports research funding from AbbVie, AstraZeneca, BeiGene, Johnson & Johnson, and Lilly; and advisory boards for AbbVie, AstraZeneca, BeiGene, and Johnson & Johnson. MS reports consultancies, honoraria, travel grants, and advisory boards for AbbVie, AstraZeneca, and Johnson & Johnson; advisory board for Swixx Pharma; and travel grants from Eli Lilly. SV reports speaker fees and nonfinancial support from AbbVie, AstraZeneca, Johnson & Johnson, Novartis, Pfizer, Roche, Sanofi, and Takeda; and serving as an investigator for clinical trials for AbbVie, AstraZeneca, Johnson & Johnson, MSD, Novartis, Pfizer, Roche, Sanofi, and Takeda. VV reports advisory boards and lecturing for AbbVie, Biocad, Johnson & Johnson, Roche, Sanofi, and Takeda; and lecturing for Astellas, AstraZeneca, and Novartis. LY reports as advisory board and research grants from AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Johnson & Johnson, and Roche. NS and CK are employees of Johnson & Johnson. KB, NT, and BL are employees of Johnson & Johnson and have stock options. BL is also a stockholder in a portfolio that at times includes other pharmaceutical and health care-related companies. APK reports advisory boards, research collaborations, and research support from AbbVie, AstraZeneca, Bristol Myers Squibb, Genmab, Johnson & Johnson, LAVA, and Roche\/Genentech; steering committees for AstraZeneca, Genmab, Johnson & Johnson, LAVA, and Roche\/Genentech; and speaker fees from AbbVie.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}