Health-Related Quality of Life and Symptoms in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma Treated with Odronextamab Monotherapy in the Phase 2 ELM-2 Study

Abstract

Background. Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have poor prognosis and significant impairment of health-related quality of life (HRQoL). CD20xCD3 bispecific antibodies show promise in the management of R/R DLBCL. ELM-2 (NCT03888105), a Phase 2, open-label, multicohort, multicenter study of the CD20xCD3 bispecific antibody odronextamab, demonstrated deep and durable responses and generally manageable safety in patients with R/R DLBCL. We report herein, for the first time, patient-reported outcome (PRO) results for patients in the R/R DLBCL cohort in ELM-2. Methods. In ELM-2, patients with R/R DLBCLafter 2 or more prior lines of therapy received odronextamab IV weekly in 21-day cycles in Cycles (C) 1-4. Revisions to the step-up dosing regimen to mitigate cytokine release syndrome (CRS) were reported previously. Odronextamab was administered with steroid prophylaxis and step-up doses of 0.7/4/20 mg in C1, then 160 mg on Days 1, 8, and 15 of C2-4 (the DLBCL 160 mg cohort). After C4, odronextamab maintenance treatment continued at 320 mg every 2 weeks until disease progression or unacceptable toxicity. Patients with durable complete response for ≥9 months transitioned to dosing every 4 weeks. PRO data were collected via the FACT-Lym, EORTC QLQ-C30, and EQ-5D-3L questionnaires at Weeks 1 (baseline), 2, 3, 4, and 10, then every 8 weeks in the first year and every 12 weeks in the second year. Pre-specified PRO analyses reported here are FACT-Lym lymphoma symptoms (LymS), FACT-G total, Trial Outcome Index (TOI), FACT-Lym total, EORTC QLQ-C30 general health status/quality of life (GHS/QoL), and EQ-5D-3L visual analog scale (VAS). PRO longitudinal analysis using mixed models for repeated measures (MMRM) were conducted through Week 42, the last visit with ≥10 patients with PRO data, and changes from baseline were statistically significant if the 95% confidence interval did not contain zero. No adjustment for multiplicity was performed, hence all statistical significance is nominal. Published ranges for minimum important difference (MID) for clinically meaningful thresholds are: GHS/QoL, 10; LymS, 2.9-5.4; FACT-G total, 3-7; TOI: 5.5-11; FACT-Lym total, 6.5-11.2; and EQ-5D-3L VAS, 7-12. Responder analysis and time to definitive deterioration (TTDD) used the upper end of these MID ranges to define clinically meaningful changes. Results. The final analysis of the DLBCL 160 mg cohort in ELM-2 assessed 141 patients. Median age was 66.0 (range, 24-88) years, with 56.0% ≥65 years, 59.6% male, 43.3% White, 47.5% Asian, 32.6% ECOG=0, and 67.4% ECOG=1. Median duration of follow-up was 26.2 (range, 8.5-34.3) months. PRO completion rates for FACT-Lym, EORTC QLQ-C30, and EQ-5D-3L were high at baseline and for most assessments through Week 42. Patients reported statistically significant and clinically meaningful improvements from Weeks 10 through 42 for FACT-Lym LymS (Figure), and from Weeks 18 through 42 for FACT-G total, FACT-Lym TOI, and FACT-Lym total (except Week 34 for FACT-G total and FACT-Lym total). Additionally, patients reported statistically significant and clinically meaningful improvements for EORTC QLQ-C30 GHS/QoL at Week 42, and for EQ-5D-3L VAS at Week 26. In responder analyses, the proportion of patients reporting clinically meaningful improvement or stability was higher than the proportion reporting meaningful worsening at each assessment through Week 42 for all scales/summary scores. Median TTDD was not reached for FACT-Lym LymS, FACT-Lym TOI, or EQ-5D-3L VAS. Conclusions. In the Phase 2 ELM-2 study, patients with R/R DLBCL reported favorable HRQoL during odronextamab treatment; patient-reported symptoms, functioning, and overall quality of life were maintained or improved from baseline through Week 42. Odronextamab treatment until disease progression may have benefits on HRQoL for heavily pretreated patients with R/R DLBCL and potentially addresses unmet needs in a challenging treatment setting. Collection of PROs was consistently high and the results offer important patient-centered insights into the overall benefit-risk profile of odronextamab in R/R DLBCL.