Reaney, Matthew D.

Background: Goals of patient-centered care for management of relapsed or refractory follicular lymphoma (R/R FL) are to improve clinical outcomes while maintaining or improving health-related quality of life (HRQoL). In ELM-2 (NCT03888105), a Phase 2, open-label, multicohort, multicenter study, odronextamab monotherapy demonstrated high and durable complete response rates and generally manageable safety in patients with R/R FL. We report here, for the first time, patient-reported outcome (PRO) results from ELM-2 in patients with R/R FL. Methods: Patients with R/R FL Grade 1-3a received odronextamab IV at 80 mg weekly in 21-day cycles in Cycles (C) 1-4. Optimization of the step-up regimen to mitigate cytokine release syndrome (CRS) was reported previously. Odronextamab was administered with steroid prophylaxis and step-up doses of 0.7/4/20 mg in C1, then 80 mg on Days 1, 8, and 15 of C2-4. After C4, odronextamab maintenance continued at 160 mg every 2 weeks until disease progression or unacceptable toxicity. Patients with durable complete response (≥9 months) switched to dosing every 4 weeks. Patients completed EORTC QLQ-C30, FACT-Lym, and EQ-5D-3L questionnaires at Weeks 1 (baseline), 2, 3, 4, and 10, then every 8 weeks for the remainder of the first year and every 12 weeks in the second year. Results here focus on six key PRO scales: EORTC QLQ-C30 Global Health Status/Quality of Life (GHS/QOL), physical functioning (PF), role functioning (RF), and fatigue; FACT-Lym lymphoma subscale (LymS); and EQ-5D-3L visual analog score (VAS). Longitudinal analyses using mixed models for repeated measures (MMRM) were conducted through Week 50 (the last visit with ≥10 patients with PRO data). Changes from baseline were considered 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) to define clinically meaningful changes are: EORTC QLQ-C30 scales, 10 points; FACT-Lym LymS, 2.9-5.4 points; and EQ-5D-3L VAS, 7-12 points. For responder and time to definitive deterioration (TTDD) analyses, the upper end of these published MID ranges was used to define deterioration or improvement. Results: At the ELM-2 interim data cutoff on 31-Jan-2023, 140 patients with R/R FL Grade 1-3a had received at least 1 dose of odronextamab. Median age was 60.5 years (range: 22-84), with 38.6% ≥65 years, 52.9% male, 57.1% White, 32.1% Asian, 52.2% ECOG=0, and 47.1% ECOG=1. Median duration of follow-up was 26.6 months (range: 6.2-37.5). PRO completion rates for EORTC-QLQ-C30, FACT-Lym, and EQ-5D-3L were high at baseline and remained high for all assessments through Week 50. At baseline, moderate levels of general health (GHS/QoL) and high levels of functioning (PF and RF) were observed that were higher (better) than reference values for general cancer or non-Hodgkin's Lymphoma (NHL). Fatigue scores at baseline were lower (less symptoms) than reference values for general cancer or NHL. EORTC QLQ-C30 GHS/QOL, PF, RF, and fatigue scores were maintained from baseline through Week 50 (Table). For EQ-5D-3L VAS, the overall estimated mean changes from baseline improved statistically significantly but did not reach MID thresholds (Table). For FACT-Lym LymS, overall estimated mean change from baseline statistically significantly improved, and scores improved statistically significantly from Weeks 10 to 42 (except Week 34), with clinically meaningful improvements at Weeks 26 and 42 (Figure). The proportion of patients reporting meaningful improvement or stability across the six scales was higher than the proportion reporting meaningful worsening through Week 50 (Table). The median TTDD for EORTC-QLQ-C30 GHS/QoL was 22.41 (95% CI: 14.59 to not yet reached) months, corresponding to the median PFS. Median TTDD was not reached for EORTC QLQ-C30 PF, FACT-Lym LymS, and EQ-5D-3L VAS scales. Conclusions: For patients with R/R FL, patient-reported HRQoL results were favorable during odronextamab treatment until disease progression, with no detriments on patient-reported symptoms, functioning, and overall quality of life. These results complement encouraging clinical efficacy, durability of responses, and tolerability observed in this highly refractory patient population and support the future role of odronextamab in the management of patients with R/R FL.

9566 Background: Cemiplimab-rwlc is the first immunotherapy to receive approval in the US, fully for pts with laBCC and accelerated for metastatic BCC, post hedgehog inhibitors or for whom hedgehog inhibitors are not appropriate. Cemiplimab resulted in clinically meaningful anti-tumor activity in pts with laBCC who progressed on or were intolerant to hedgehog inhibitor therapy (NCT03132636). This analysis evaluated HRQoL in these pts. Methods: Adults with laBCC and ECOG performance status ≤1 (n=84) received IV cemiplimab 350 mg Q3W for up to 9 treatment cycles. At baseline (BL) and day 1 of each cycle (C), pts completed EORTC QLQ-C30 and SKINDEX-16 questionnaires that assess Global Health Status (GHS)/QoL, functioning, and BCC-related symptoms. Mixed-effects repeated measures (MMRM) models were used to estimate least squares (LS) mean (standard error [SE]) change from BL during treatment (i.e., across C2 to C9); changes ≥|10| points were considered clinically meaningful. Responder analyses were conducted in pts with non-missing data from BL to determine the proportions with clinically meaningful improvement or deterioration, or stability on QLQ-C30 and SKINDEX-16 at C2 and C9; a 10-point threshold was considered meaningful for both instruments. Results: BL scores showed moderate to high levels of functioning and low symptom burden. In MMRM models, overall changes from BL on QLQ-C30 indicated stability for GHS/QoL and all scales except for clinically meaningful worsening of fatigue (LS mean [SE] change 12.5 [3.9]; P<.05). In responder analysis, the majority of pts reported clinically meaningful improvement or stability at C2 and C9 on all QLQ-C30 functioning scales and the key symptom of pain but not fatigue (Table). On SKINDEX-16, MMRM models showed clinically meaningful improvement on the emotional subscale (LS mean [SE] change –13.2 [3.9]; P<.05) and stability on the symptom and functional subscales. Responder analysis showed clinically meaningful improvements or stability across the SKINDEX-16 subscales in approximately 80% of pts at C2, and 70–80% of pts at C9. Conclusions: In laBCC pts treated with cemiplimab, the majority reported clinically meaningful improvement or stability in GHS/QoL and functional status while maintaining a low symptom burden except for fatigue. Clinical trial information: NCT03132636. [Table: see text]