Researchers used data from the POLARIX study to compare patient-reported outcomes (PROs) against clinician-reported adverse event (AE) data and found that several AEs were underreported by clinicians. Carrie Thompson, MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues, published their findings in Blood.
“These [health-related quality of life] data underscore the complementarity of PROs, as an adjunct to clinician-reported AEs, in evaluating the efficacy and tolerability of new treatments,” the authors noted.
The international, randomized, double-blind, placebo-controlled, phase 3 POLARIX study observed improved progression-free survival in patients with diffuse large B-cell lymphoma (DLBCL) treated with Pola-R-CHP (polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone) compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).
This substudy evaluated PRO data to “characterize the patient experience” of treatment in 874 patients. Researchers used the EORTC QLQ-C30 (30 questions) and FACT-Lym (42 items) to evaluate disease- and treatment-related symptoms. Information was collected on day one of cycles one, two, three, and five, at the end of treatment, biannually for two years after treatment, and annually for three more years.
Symptoms of fatigue, diarrhea, constipation, nausea, and vomiting were reported in higher incidence by PROs (>50%) compared with clinician-reported AEs (<30%). Clinicians also tended to report AEs as lower-grade compared with PRO data.
Gastrointestinal symptoms (eg, diarrhea, constipation, nausea, and vomiting) were similar between treatment arms at baseline, but between cycle two and the end of treatment, diarrhea was more frequently reported in patients treated with Pola-R-CHP (range, 17-34%) than R-CHOP (range, 18-24%). Constipation, however, was more frequently reported in the R-CHOP group (range, 21-42% vs 23-35%, respectively). Both symptoms returned to baseline levels or improved from baseline at the end of treatment. Nausea and vomiting were infrequently in both treatment cohorts and returned to baseline levels at the end of treatment.
Quality of life, functional scales, and fatigue were similar in both cohorts, and clinically meaningful improvements were observed with both treatments, sustained during treatment, and plateaued after treatment.
Both treatments induced “rapid” improvements in lymphoma symptom scores, with clinically meaningful improvements observed in 82.3% of Pola-R-CHP patients and 81.3% of R-CHOP patients.
The authors indicated that the “discordance” between patient- and clinician-reported AEs was “not previously reported in the setting of DLBCL.”
The study is limited by its omission of PRO data for patients experiencing disease progression.
“Incorporation of PROs into clinical studies, alongside standard clinician-reported AEs, is essential for a comprehensive assessment of treatment efficacy and tolerability, and should be standardized as part of regulatory approvals,” the authors concluded.
Reference
Thompson C, Trněný M, Morschhauser F, et al. PROs vs clinician-reported adverse events in a large clinical trial: findings from the phase 3 POLARIX study. Blood. 2026;147(3):254-265. doi:10.1182/blood.2025028848
