Background: Brentuximab vedotin (BV) with AVE-PC (Adriamycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide) demonstrated superior efficacy to standard therapy (Castellino, NEJM 2022) and was associated with better HRQoL for pediatric patients with high-risk HL in the COG-led AHOD 1331 trial (Williams, JCO 2024). As mean estimates of HRQoL may not capture individual participants’ heterogeneity, we aimed to identify and describe subgroups of participants with similar HRQoL trajectories over time from study entry to end of therapy.
Methods: Eligibility for AHOD1331 included previously untreated pediatric HL with stage IIB + bulk, IIIB, IVA, or IVB. 268 participants aged 11+ enrolled in a prespecified longitudinal patient-reported outcomes substudy completed the 7-item Child Health Ratings Inventories (CHRIs)–Global scale (HRQoL) prior to treatment, after cycle 2, after cycle 5, and at the end of treatment. Group-based trajectory models identified latent clusters of individuals with similar HRQoL patterns over time. The number of groups was selected based on model fit statistics, clinical interpretability, and size. Multivariate multinomial logistic regression estimated associations between a priori defined characteristics and groups. Kaplan Meier curves with log-rank tests examined differences in post-treatment progression-free survival (PT-PFS) by group.
Results: Three groups were identified (Figure 1): consistently favorable HRQoL (n=79), moderate and improving HRQoL (n=119), and consistently unfavorable HRQoL (n=70). Older age (OR [95%CI] 1.35 [1.10-1.66] p=0.005), female sex (2.72 [1.27, 5.84] p=0.010), Hispanic ethnicity (2.65 [1.00-7.07] p=0.051), and B-symptoms (2.39 [1.02-5.62] p=0.045) were associated with increased odds of membership in the consistently unfavorable group vs the consistently favorable group. Age (1.25 [1.06-1.49] p=0.010) and B-symptoms (2.48 [1.20-5.12] p=0.014) were associated with membership in the moderate and improving trajectory group. Group membership was not associated with PT-PFS in either study arm (BV arm, p=0.115) or standard arm (p=0.265).
Conclusions: A subgroup of patients with high-risk pediatric HL experience persistently poor HRQoL that appears to begin at diagnosis and continue throughout therapy. Pre-treatment factors such as age, female sex, and B-symptoms were associated with worse HRQoL trajectories. These findings may help to identify patients more at risk for poor HRQoL and need intervention.
AnnaLynn Williams, Angie Mae Rodday, Lindsay A. Renfro, Yue Wu, Tara O. Henderson, Frank G. Keller, Kara Kelly, Sharon M. Castellino, Susan K. Parsons