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Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized phase 3 CLL14 study

Affiliations
  • 1Department I of Internal Medicine, Faculty of Medicine and University Hospital of Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, German Chronic Lymphocytic Leukemia Study Group, University of Cologne, Cologne, Germany.
  • 2F. Hoffmann-La Roche Ltd., Basel, Switzerland.
  • 3F. Hoffmann-La Roche Ltd, Mississauga, ON, Canada.
  • 4Division of CLL, Department III of Internal Medicine, University Hospital Ulm, Ulm, Germany.
  • 5Universitätsklinikum Schleswig Holstein, Kiel, Germany.
  • 6Multiprofile Hospital for Active Treatment Pazardjik, Pazardzhik, Bulgaria.
  • 7Rigshospitalet, Copenhagen, Denmark.
  • 8Box Hill Hospital, Box Hill, VIC, Australia.
  • 9Hospital De La Princesa, Madrid, Spain.
  • 10Te Rerenga Ora Wellington Blood and Cancer Centre, Te Whatu Ora Health New Zealand Capital, Wellington, New Zealand.
  • 11Cancer Immunotherapy Program, Malaghan Institute of Medical Research, Wellington, New Zealand.
  • 12Evangelisches Krankenhaus Herne, Herne, Germany.
  • 13Palmerston North Hospital, Palmerston North, New Zealand.
  • 14AbbVie Inc, Chicago, IL.
  • 15Genentech Inc, South San Francisco, CA.
  • 16F. Hoffmann-La Roche Ltd, Welwyn, United Kingdom.

Published on:

July 31, 2024

Abstract

In the CLL14 study, patients with previously untreated chronic lymphocytic leukemia (CLL) and coexisting conditions were randomized to 12 cycles of venetoclax-obinutuzumab (Ven-Obi, n = 216) or chlorambucil-obinutuzumab (Clb-Obi, n = 216). Progression-free survival (PFS) was the primary end point. Key secondary end points included time-to-next-treatment (TTNT), rates of undetectable minimal residual disease (uMRD), overall survival (OS), and rates of adverse events. Patient reported outcomes of time until definitive deterioration (TUDD) in quality of life (QoL) were analyzed. At a median observation time of 76.4 months, PFS remained superior for Ven-Obi compared with Clb-Obi (median, 76.2 vs 36.4 months; hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.31-0.52; P < .0001). Likewise, TTNT was longer after Ven-Obi (6-year TTNT, 65.2% vs 37.1%; HR, 0.44; 95% CI, 0.33-0.58; P < .0001). In the Ven-Obi arm, presence of del(17p), unmutated immunoglobulin heavy-chain variable region, and lymph node size of ≥5 cm were independent prognostic factors for shorter PFS. The 6-year OS rate was 78.7% in the Ven-Obi and 69.2% in the Clb-Obi arm (HR, 0.69; 95% CI, 0.48-1.01; P = .052). A significantly longer TUDD in global health status/QoL was observed in the Ven-Obi than in the Clb-Obi arm (median, 82.1 vs 65.1 months; HR, 0.70; 95% CI, 0.51-0.97). Follow-up-adjusted second primary malignancies incidence rates were 2.3 and 1.4 per 1000 patient-months in the Ven-Obi and Clb-Obi arm, respectively. The sustained long-term survival and QoL benefits support the use of 1-year fixed-duration Ven-Obi in CLL. This trial was registered at www.ClinicalTrials.gov as #NCT02242942.

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