Chemotherapy-free combination of ibrutinib and obinutuzumab for untreated advanced follicular lymphoma: results of a phase II study from the German Lymphoma Alliance

Schmidt, Christian; Scheubeck, Gabriel ; Jurinovic, Vindi ; Sökler, Martin; Forstpointner, Roswitha; Buske, Christian; Viardot, Andreas; Keller, Ulrich; Graeven, Ullrich; Marks, Reinhard; Hänel, Mathias; Liersch, Rüdiger; Dürig, Jan; Pott, Christiane; Hoster, Eva ; Unterhalt, Michael und Hiddemann, Wolfgang (2025): Chemotherapy-free combination of ibrutinib and obinutuzumab for untreated advanced follicular lymphoma: results of a phase II study from the German Lymphoma Alliance. In: Haematologica, Bd. 110, Nr. 12: S. 3022-3031

Abstract

Immunochemotherapy induces long-term responses in patients with follicular lymphoma. However, the toxicity of chemotherapy remains a relevant challenge. The Bruton tyrosine kinase inhibitor ibrutinib has shown significant activity in patients with indolent B-cell lymphoma. Combining ibrutinib with obinutuzumab may, therefore, be an attractive chemotherapy-free option. We conducted a prospective, single-arm, multicenter phase II trial to evaluate the chemotherapy-free regimen of obinutuzumab plus ibrutinib in patients with previously untreated advanced-stage follicular lymphoma. Patients received six 21-day cycles of ibrutinib and obinutuzumab for induction and 12 additional 2-month cycles for maintenance. The primary endpoint was 1-year progression-free survival (PFS). The study was powered to detect an improvement of 10% over the 1-year PFS of 85%. Ninety-eight patients were enrolled in the trial. The median follow-up was 5.5 years. After induction, five patients (5%) had a complete response and 82 (85%) had a partial response. The 1-year PFS was 80%, missing the prospected improvement of a 1-year PFS of 85% (P=0.93). The median PFS was 4.5 years; median duration of response and overall survival were not reached. The most common adverse events of grade 3/4 were neutropenia, lung infection, hypertension, fatigue, rash and thrombocytopenia. The trial of a chemotherapy-free regimen of obinutuzumab and ibrutinib in follicular lymphoma patients failed to demonstrate a 10% improvement in the primary efficacy endpoint. However, the combination produced durable and deep responses and had an acceptable safety profile. Trial registration, EudraCT-Number: 2014-005164-15.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie ; Medizin > Klinikum der LMU München > Medizinische Klinik und Poliklinik III (Onkologie)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0390-6078
• Sprache: Englisch