Max S Topp1, Herbert Eradat2, Axel Florschütz3, Andreas Hochhaus4, Tomasz Wrobel5, Jan Walewski6, Wanda Knopinska-Posluszny7, Abraham S Kanate8, Ewa Lech-Maranda9, Uta Brunnberg10, Surya Chitra11, Tina G Nielsen12, Gila Sellam12, Mahesh Shivhare13, Izidore S Lossos14. 1. Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Anstalt des öffentlichen Rechts, Josef-Schneider-Straße 2, 97080, Würzburg, Germany. topp_m@ukw.de. 2. Division of Hematology-Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. 3. Städtisches Klinikum Dessau, Dessau-Roβlau, Germany. 4. Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany. 5. Department of Hematology, Wrocław Medical University, Wrocław, Poland. 6. Narodowy Instytut Onkologii im, Marii Skłodowskiej-Curie - Panstwowy Instytut Badawczy, Warsaw, Poland. 7. Uniwersytet Warmińsko-Mazurski, Olsztynie, Poland. 8. West Virginia University Cancer Institute, Morgantown, WV, USA. 9. Institute of Hematology and Transfusion Medicine, Warsaw, Poland. 10. Universitätsklinikum Frankfurt, Frankfurt, Germany. 11. Genentech, Inc., South San Francisco, CA, USA. 12. F. Hoffmann-La Roche Ltd, Basel, Switzerland. 13. Roche Products Limited, Welwyn Garden City, UK. 14. Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
Abstract
PURPOSE: New therapies are needed for relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma. This phase 1b, open-label trial evaluated two anti-CD20-based triplet combinations. METHODS: Patients with R/R follicular lymphoma (FL; n = 13) were treated with obinutuzumab, atezolizumab, and polatuzumab vedotin (G-atezo-pola; 1.4 mg/kg/1.8 mg/kg) and patients with R/R diffuse large B-cell lymphoma (DLBCL; n = 23) received rituximab (R)-atezo-pola. The primary efficacy endpoint was complete response (CR) at end of induction (EOI) by PET-CT (investigator assessed; modified Lugano 2014 criteria). Safety endpoints were also assessed. RESULTS: 13 FL patients were treated and evaluable for safety; 2/23 DLBCL patients did not receive treatment and were not included in the safety population. Median observation time was 23.3 and 5.7 months in the FL and DLBCL cohorts, respectively. At EOI, CR rates in FL patients treated with G-atezo-pola at pola doses of 1.4 mg/kg (N = 3) and 1.8 mg/kg (N = 7) were 33% and 14%, respectively. In DLBCL patients receiving R-atezo-pola, the CR rate at EOI was 13%. In the FL cohort, 62% of patients experienced a grade 3-5 adverse event (AE; including two deaths) and 31% developed a serious AE (SAE). In DLBCL patients, R-atezo-pola was associated with a lower incidence of grade 3-5 AEs (24%; one death) and SAEs (10%). In both cohorts, the most common grade 3-5 AEs were hematologic toxicities. CONCLUSION: Based on these safety issues, considered as related specifically to G-atezo-pola, and limited efficacy, no further development of either combination is planned. TRIAL REGISTRATION: NCT02729896; Date of registration: April 6, 2016.
PURPOSE: New therapies are needed for relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma. This phase 1b, open-label trial evaluated two anti-CD20-based triplet combinations. METHODS: Patients with R/R follicular lymphoma (FL; n = 13) were treated with obinutuzumab, atezolizumab, and polatuzumab vedotin (G-atezo-pola; 1.4 mg/kg/1.8 mg/kg) and patients with R/R diffuse large B-cell lymphoma (DLBCL; n = 23) received rituximab (R)-atezo-pola. The primary efficacy endpoint was complete response (CR) at end of induction (EOI) by PET-CT (investigator assessed; modified Lugano 2014 criteria). Safety endpoints were also assessed. RESULTS: 13 FL patients were treated and evaluable for safety; 2/23 DLBCL patients did not receive treatment and were not included in the safety population. Median observation time was 23.3 and 5.7 months in the FL and DLBCL cohorts, respectively. At EOI, CR rates in FL patients treated with G-atezo-pola at pola doses of 1.4 mg/kg (N = 3) and 1.8 mg/kg (N = 7) were 33% and 14%, respectively. In DLBCL patients receiving R-atezo-pola, the CR rate at EOI was 13%. In the FL cohort, 62% of patients experienced a grade 3-5 adverse event (AE; including two deaths) and 31% developed a serious AE (SAE). In DLBCL patients, R-atezo-pola was associated with a lower incidence of grade 3-5 AEs (24%; one death) and SAEs (10%). In both cohorts, the most common grade 3-5 AEs were hematologic toxicities. CONCLUSION: Based on these safety issues, considered as related specifically to G-atezo-pola, and limited efficacy, no further development of either combination is planned. TRIAL REGISTRATION: NCT02729896; Date of registration: April 6, 2016.
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