Primary Results of Patient-Reported Outcomes in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Treated with Glofitamab Plus Gemcitabine and Oxaliplatin (Glofit-GemOx) Versus Rituximab Plus GemOx (R-GemOx) from the Phase III Starglo Study
Authors: Gregory Gareth P. , Abramson Jeremy S. , Huang Hui-Qiang , Zhang Qing-Yuan , Ku Matthew , Yoon Dok Hyun , Fox Christopher P. , Abdulhaq Haifaa , Townsend William , Ashby Joan , Harris Alana , Orellana-Noia Victor , Simko Stephen , Kallemeijn Martine , Ta Richard , Relf James , Huang Huang , Lundberg Linda , Zhang Huilai 
Published: December 2024

Background: Patients (pts) with lymphoma have reduced health-related quality of life (HRQoL) due to disease- and treatment-related symptoms, which declines at the time of progression and with further lines of treatment. Glofitamab (Glofit) is the first CD20xCD3 bispecific antibody to demonstrate survival benefit in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in a randomized Phase III trial (STARGLO; NCT04408638). In this study, Glofit-GemOx showed statistically significant benefit in overall and progression-free survival, as well as complete response rate, over R-GemOx in pts with R/R DLBCL who were ineligible for autologous stem cell transplant (Abramson, et al. EHA 2024). Here, we use patient-reported outcomes (PRO) to capture the impact of treatment on HRQoL in pts from the STARGLO trial.
Methods: Pts were randomized 2:1 to receive either Glofit-GemOx (8 cycles, plus 4 cycles of Glofit monotherapy) or R-GemOx (8 cycles). HRQoL was measured using the Functional Assessment of Cancer Treatment-Lymphoma Lymphoma Subscale (FACT-Lym LYMS; scale range 0-60; high score = less lymphoma symptoms) for lymphoma symptoms and the European Organization for Research and Treatment of Cancer Quality of Life-Core 30 questionnaire (EORTC QLQ-C30; scale range 0-100; high score = better functioning and worse symptoms) for functioning and generic symptom scales. Pts completed questionnaires during treatment (Day 1 of Cycles [C]1-5, 7, 9 and 11), at end of treatment (EOT), and every 3 months until death or loss to follow-up. Questionnaire compliance, time to deterioration (TTD), change from baseline (CfB) and summary statistics were estimated at each assessment time point. For TTD analyses, clinically meaningful worsening from baseline for physical functioning (≥10-point decrease), fatigue (≥10-point increase), and lymphoma symptom scores (≥3-point decrease) were reported based on validated thresholds.
Results: In total, 274 pts with DLBCL were enrolled (Glofit-GemOx, n=183; R-GemOx, n=91); 172 (62.8%) after 1 prior therapy and 102 (37.2%) after ≥2 prior therapies. Overall, 153 (55.8%) pts had primary refractory disease, and 166 (60.6%) pts were refractory to last therapy. PRO questionnaire response rates were high (&gt;95%) while on treatment.
At baseline, pts in both arms reported moderate-to-high functioning, mild impairment in global health status/QoL, and low to low-moderate levels of lymphoma symptoms as assessed by the FACT-Lym LYMS, as well as low-to-mild symptom severity as measured by the EORTC QLQ-C30.
The median TTD was comparable between arms (Glofit-GemOx vs R-GemOx) for fatigue (1.6 vs 4.0 months), physical functioning (23.0 vs 18.0 months), and lymphoma symptoms (6.2 vs 4.5 months). At C3, CfB improvements in pain (Glofit-GemOx: −11.38; R-GemOx: −6.67) and lymphoma symptoms (Glofit-GemOx: 3.14; R-GemOx: 0.87) for Glofit-GemOx surpassed the minimal clinically important difference (MCID; pain: −10.0; lymphoma symptoms: 3.0). By C5, improvements continued to surpass the MCID in both arms; mean CfB in the Glofit-GemOx and R-GemOx arms were −12.33 and −12.75 for pain, and 2.27 vs 5.92 for lymphoma symptoms, respectively. At EOT, both arms had sustained improvements in overall pain scores (Glofit-GemOx: 15.94; R-GemOx: 28.04) and lymphoma symptom scores (Glofit-GemOx: 48.78; R-GemOx: 45.13), with pts in the Glofit-GemOx arm reporting less pain and fewer lymphoma symptoms than those in the R-GemOx arm.
Conclusions: In the STARGLO study, HRQoL results were comparable between arms, even with a longer treatment period and higher rates of adverse events in the Glofit-GemOx arm. Together with the significant survival benefit conferred on pts with Glofit-GemOx over R-GemOx observed in the STARGLO trial, these HRQoL data further support the use of Glofit-GemOx as a new treatment option for pts with R/R DLBCL.