Health-related quality of life and symptoms in patients with rituximab-refractory indolent non-Hodgkin lymphoma treated in the phase III GADOLIN study with obinutuzumab plus bendamustine versus bendamustine alone.

We present health-related quality of life (HRQoL) data from GADOLIN, comparing bendamustine (B) alone or combined with obinutuzumab (G-B) in rituximab-refractory indolent non-Hodgkin lymphoma patients. The Functional Assessment of Cancer Treatment-Lymphoma (FACT-Lym) questionnaire was administered on day 1 of cycles 1, 3, and 5 during treatment, at end of induction (EOI), bi-monthly for 2 years during maintenance/follow-up, and annually during extended follow-up until progression/death. Time to first ≥6-point worsening from baseline in the FACT-Lym trial outcome index (TOI) was estimated. Minimally important differences at individual subscale and total score level were used to define the proportion of patients reporting improvement on the FACT-Lym lymphoma-specific subscale (≥3 points), FACT-Lym TOI (≥6 points), and FACT-Lym total score (≥7 points). Overall, 396 patients were randomized. Analysis was conducted when 175 Independent Review Committee-assessed progression-free survival (PFS) events were observed. Questionnaire completion rates were generally balanced between arms at baseline, EOI, and final follow-up. Median time to ≥6-point worsening from baseline on the FACT-Lym TOI was 8.0 months in the G-B arm and 4.6 months in the B arm (HR 0.74; 95% CI 0.56-0.98). More G-B patients reported meaningful improvements on the FACT-Lym questionnaire subscales. Results were similar when follicular lymphoma patients were analyzed separately. The delayed time to worsening and greater proportion of patients reporting meaningful improvement in HRQoL in the G-B arm suggest that benefit in PFS is not at the expense of an increase in treatment-related toxicity that could lead to reduced HRQoL.
Competing Interests: Compliance with ethical standards The protocol was approved by the ethics committees of participating centers and is registered at ClinicalTrials.gov. Funding This study was sponsored by F. Hoffmann-La Roche Ltd. Conflict of interest BDC has performed in a consulting or advisory role for Celgene, Gilead, Pharmacyclics, Astra Zeneca, Spectrum, and Astellas, and his institution has received research funding from Pharmacyclics, Acerta, Seattle Genetics, and Gilead. PCT is an employee of Genentech, Inc. and owns stock in Roche/Genentech. JGG has received honoraria from Roche/Genentech, Celgene, Pharmacyclis, Janssen, Gilead, Mundipharma, TG Therapeutics, and Acerta. ND is an employee of Roche and owns stock in Roche and GSK. EK has received honoraria from Janssen, Gilead, Celgene, and AbbVie; has performed in a consulting or advisory role for Janssen, Baxalta, and AbbVie; and has received research funding and drug support from—and worked on transitional research with—Pfizer. PJL has performed in a consulting or advisory role for Celgene, Mundipharma, and Servier. CT has performed in a consulting or advisory role for Janssen, Gilead, and Roche and has received travel, accommodation, and expenses support from Janssen and Gilead. EW-F is an employee of F. Hoffmann-La Roche Ltd. AL is an employee of F. Hoffmann-La Roche Ltd., owns stock in Novartis, and has received travel, accommodation, and expenses support from Roche and Novartis. LHS has received honoraria from Roche/Genentech, Celgene, Seattle Genetics, AbbVie, Janssen, Gilead, Amgen, and TG Therapeutics and has performed in a consulting or advisory role for Roche/Genentech, Celgene, Gilead, Janssen, Pfizer, Amgen, Seattle Genetics, AbbVie, Lundbeck, and TG Therapeutics. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individual participants included in the study.