Beyond Survival: Measuring Treatment Tolerability with Patient-Reported Outcomes in the Lymphoma Immunotherapy Era

Immunotherapeutic strategies for the treatment of lymphomas are rapidly expanding and can deliver durable remissions to patients with historically limited treatment options. Patient-reported outcomes (PROs) provide direct measurement of symptoms, functioning, and health-related quality of life (HRQoL), complementing physician-assessed toxicities and enabling a more comprehensive assessment of "treatment tolerability," defined as the willingness of patients to adhere to treatment dose and schedule based on symptom burden and functioning. In this review, we demonstrate that when PROs are incorporated into clinical research, we gain a better understanding of treatment tolerability, particularly of novel immunotherapies, which confer distinct toxicity profiles compared with traditional chemoimmunotherapy. As survival improves, we argue that PROs should be incorporated as a primary or co-primary endpoint in most modern clinical trials, rather than as a point of interest in exploratory analyses.

In patients with lymphoma, baseline and longitudinal HRQoL are prognostic of progression-free and overall survival. However, persistent discordance between clinician-graded adverse events (AEs) and patient-reported symptomatic AEs suggests that current trial endpoints focused primarily on safety and survival incompletely capture the patient experience, particularly in the context of novel immunotherapy-related toxicities. PROs are essential for interpreting modern lymphoma immunotherapies, where acute and chronic toxicities coexist with the promise of long-term remissions. Despite broad consensus of their utility, PRO analysis from seminal lymphoma immunotherapy trials remains inconsistent, and there remain significant gaps in the literature regarding the true patient-reported tolerability of emerging therapeutic regimens. Future trials should adopt harmonized PRO strategies (including symptom and functional domains), define meaningful thresholds for minimally important differences, and integrate real-world PRO data prospectively to better align clinical trial data with patient-centered treatment tolerability.