TY - JOUR
T1 - MRD response in relapsed/refractory FL after obinutuzumab plus bendamustine or bendamustine alone in the GADOLIN trial
AU - Pott, Christiane
AU - Sehn, Laurie H.
AU - Belada, David
AU - Gribben, John
AU - Hoster, Eva
AU - Kahl, Brad
AU - Kehden, Britta
AU - Nicolas-Virelizier, Emmanuelle
AU - Spielewoy, Nathalie
AU - Fingerle-Rowson, Guenter
AU - Harbron, Chris
AU - Mundt, Kirsten
AU - Wassner-Fritsch, Elisabeth
AU - Cheson, Bruce D.
N1 - Funding Information:
Gilead Sciences, and Janssen-Cilag. ND, GFR, CH, EWF, and KM are employees of and own stock in F. Hoffmann-La Roche Ltd. JG reports advisory board membership and research funding from Roche/Gen-entech, advisory board membership for Abbvie, and speakers’ fees, research funding and advisory board membership for Janssen, Acerta, Pharmacyclics, and TG Therapeutics. EH reports travel support from Roche Pharma AG. B Kahl reports advisory board membership for F. Hoffmann-La Roche Ltd. B Kehden and ENV report no conflict of interest. LHS reports consultancy fees for Roche/Genentech, Amgen, Lundbeck, Seattle Genetics, Janssen, Celgene, Abbvie, and TG Therapeutics. BDC reports advisory board membership for Roche/ Genentech, Abbvie, and Acerta and research funding to his institution from F. Hoffmann-La Roche Ltd/Genentech Inc.
Funding Information:
Acknowledgements The authors would like to thank the patients and their families, along with the study investigators, study coordinators, and nurses. GADOLIN was sponsored by F. Hoffmann-La Roche Ltd/ Genentech Inc. We would like to acknowledge the contributions of Gregg Fine, Jane Huang, and Michael Wenger to the protocol design and initial study set up. Third-party Medical Writing assistance, under the direction of CP, was provided by Lynda McEvoy, and Helen Cathro of Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd.
Publisher Copyright:
© 2019, The Author(s).
PY - 2020/2/1
Y1 - 2020/2/1
N2 - We report assessment of minimal residual disease (MRD) status and its association with outcome in rituximab-refractory follicular lymphoma (FL) in the randomized GADOLIN trial (NCT01059630). Patients received obinutuzumab (G) plus bendamustine (Benda) induction followed by G maintenance, or Benda induction alone. Patients with a clonal marker (t[14;18] translocation and/or immunoglobulin heavy or light chain rearrangement) detected at study screening were assessed for MRD at mid-induction (MI), end of induction (EOI), and every 6–24 months post-EOI/discontinuation by real-time quantitative PCR. At MI, 41/52 (79%) patients receiving G-Benda were MRD-negative vs. 17/36 (47%) patients receiving Benda alone (p = 0.0029). At EOI, 54/63 (86%) patients receiving G-Benda were MRD-negative vs. 30/55 (55%) receiving Benda alone (p = 0.0002). MRD-negative patients at EOI had improved progression-free survival (HR, 0.33, 95% CI, 0.19–0.56, p < 0.0001) and overall survival (HR, 0.39, 95% CI, 0.19–0.78, p = 0.008) vs. MRD-positive patients, and maintained their MRD-negative status for longer if they received G maintenance than if they did not. These results suggest that the addition of G to Benda-based treatment during induction can significantly contribute to the speed and depth of response, and G maintenance in MRD-negative patients potentially delays lymphoma regrowth.
AB - We report assessment of minimal residual disease (MRD) status and its association with outcome in rituximab-refractory follicular lymphoma (FL) in the randomized GADOLIN trial (NCT01059630). Patients received obinutuzumab (G) plus bendamustine (Benda) induction followed by G maintenance, or Benda induction alone. Patients with a clonal marker (t[14;18] translocation and/or immunoglobulin heavy or light chain rearrangement) detected at study screening were assessed for MRD at mid-induction (MI), end of induction (EOI), and every 6–24 months post-EOI/discontinuation by real-time quantitative PCR. At MI, 41/52 (79%) patients receiving G-Benda were MRD-negative vs. 17/36 (47%) patients receiving Benda alone (p = 0.0029). At EOI, 54/63 (86%) patients receiving G-Benda were MRD-negative vs. 30/55 (55%) receiving Benda alone (p = 0.0002). MRD-negative patients at EOI had improved progression-free survival (HR, 0.33, 95% CI, 0.19–0.56, p < 0.0001) and overall survival (HR, 0.39, 95% CI, 0.19–0.78, p = 0.008) vs. MRD-positive patients, and maintained their MRD-negative status for longer if they received G maintenance than if they did not. These results suggest that the addition of G to Benda-based treatment during induction can significantly contribute to the speed and depth of response, and G maintenance in MRD-negative patients potentially delays lymphoma regrowth.
UR - http://www.scopus.com/inward/record.url?scp=85071928413&partnerID=8YFLogxK
U2 - 10.1038/s41375-019-0559-9
DO - 10.1038/s41375-019-0559-9
M3 - Article
C2 - 31462735
AN - SCOPUS:85071928413
SN - 0887-6924
VL - 34
SP - 522
EP - 532
JO - Leukemia
JF - Leukemia
IS - 2
ER -