Flowers, Christopher R.

12100 Background: The safety profiles of novel agents are mainly based on clinician-reported adverse events (AEs) from clinical trials. Patient-reported outcomes (PROs) may better represent the treatment burden experienced by patients (pts) compared with clinician-reported AEs. Using data from POLARIX, a double-blind, placebo-controlled, randomized Phase 3 international study (NCT03274492), we previously presented PRO and clinician-reported data showing similar rates of neuropathy (Trněný et al. 2022). Here, we evaluate the reporting of other common symptoms using PRO and clinician-reported data in POLARIX. Methods: POLARIX methods were previously described (Tilly et al. 2022); this analysis included all pts with PRO data. PRO and clinician-reported data described the incidence and severity of fatigue, constipation, diarrhea, nausea, and vomiting. Clinician-reported severity grading was based on the NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.0. PROs were collected using the European Organisation Research and Treatment of Cancer Quality of Life-Core 30 questionnaire (EORTC QLQ-C30), which was administered to pts at clinic visits on Day 1 of Cycles 1 (baseline), 2, 3, and 5, and end of treatment (EOT). PRO severity scores included ‘A little’, ‘Quite a bit’, and ‘Very much’. Results: Overall, 825 pts were evaluable. From baseline to EOT, PROs showed a higher incidence of symptoms compared with clinicians for fatigue (98% vs 27%), constipation (68% vs 29%), diarrhea (56% vs 26%), nausea (58% vs 40%), and vomiting (24% vs 15%). PRO severity scores of ‘Quite a bit’ or ‘Very much’ were reported in 33% of pts for fatigue, 29% for constipation, 17% for diarrhea, 19% for nausea, and 7% for vomiting. Clinicians reported Grade ≥2 symptoms in 11% of pts for fatigue, 11% for constipation, 11% for diarrhea, 14% for nausea, and 6% for vomiting. Conclusions: In POLARIX, pts reported a higher incidence and severity of symptoms compared with clinicians. Although distinct scales were used, the differences in symptom rates reported by pts and clinicians were clinically meaningful. These data may have implications for symptom management, including physician evaluation and communication of symptom expectations for pts. Reporting of symptoms by PROs should be incorporated into clinical trials as an adjunct to standard AE reporting to better characterize the patient experience. Clinical trial information: NCT03274492 . [Table: see text]

Abstract The prognostic relevance of diagnosis to treatment interval (DTI) in patients with newly diagnosed mantle cell lymphoma (MCL) is unknown. Hence, we sought to evaluate the impact of DTI on outcomes in MCL using 3 large datasets (1) the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource, (2) patients enrolled in the ALL Age Asthma Cohort/CALGB 50403, and (3) a multisitecohort of patients with MCL. Patients were a priori divided into 2 groups, 0 to 14 days (short DTI) and 15 to 60 days (long DTI). The patients in whom observation was deemed appropriate were excluded. One thousand ninety-seven patients newly diagnosed with MCL and available DTI were included in the study. The majority (73%) had long DTI (n=797). Patients with short DTI had worse eastern cooperative oncology group performance status (ECOG PS ≥2), higher lactate dehydrogenase, bone marrow involvement, more frequent B symptoms, higher MCL International Prognostic Index (MIPI ≥6.2), and were less likely to receive intensive induction therapy than long DTI group. The median progression-free survival (2.5 years vs 4.8 years, p<0.0001) and overall survival (7.8 years vs. 11.8 years, p<0.0001) were significantly inferior in the short DTI group than the long DTI cohort and remained significant for progression-free survival and overall survival in multivariable analysis. We show that the DTI is an important prognostic factor in patients newly diagnosed with MCL and is strongly associated with adverse clinical factors and poor outcomes. DTI should be reported in all the patients newly diagnosed with MCL who are enrolling in clinical trials and steps must be taken to ensure selection bias is avoided.