Intraindividual Comparison of Recognition of Symptom Burden in MPN between Patient- and Physician-Reported Assessment and Its Impact on Survival - an Analysis By the German Study Group for MPN (GSG-MPN)

Myeloproliferative neoplasms (MPN) are associated with a variety of symptoms that severely impact patients' quality of life and ability to perform daily activities. Recent studies reported on differences in the perception of physician- versus patient-reported symptom burden. So far, direct comparisons of patient- and physician-reported scales are lacking. Moreover, impact of symptom burden on overall survival had so far shown inconclusive results. The German Study Group MPN Bioregistry is an observational study of BCR::ABL1-negative MPN patients with > 70 participating centers, including academic and community hospitals as well as office-based hematologists. Here, a prospective analysis on symptom burden of 3,979 MPN patients was conducted to intra-individually compare reports of physicians (present or absent, as documented in the medical record) versus patients (as rated on a scale of 1 to 10 using a questionnaire), collected at the same time (73% within a week). Cohen's kappa was calculated to assess the degree of agreement between patient and physician reports. Adjusted Cox models were fitted to investigate the effect of symptom burden on survival. 77% of all GSG-MPN registry patients at the time of data extraction had at least one common patient-physician symptom assessment at baseline or any follow-up visit. Characteristics of patients in our cohort were comparable to those in the whole registry. Overall, 93% reported the presence of at least one symptom at baseline. Severe symptom burden (symptom score ≥ 7) was reported in 38% of the patients (range depending on phenotype 34%-44%). Fatigue was the most prevalent symptom reported by both patients (82-85%) and physicians (26% (ET, MPN-U) to 36% (MF; p < 0.001)). Night sweats, pain and pruritus were the second most common symptoms, followed by weight loss and fever. Comparability of baseline symptom prevalence between physician and patients´ assessment was low. Even for objectively measurable symptoms, discrepancies became obvious: unintentional weight loss in the past 6 months was reported by 26% (706/2687) of patients but only 6% of physicians (169/2687). For all symptoms, patients reported a higher prevalence than physicians. Concordance was low and improved slightly for symptoms with a severity score of ³ 4. Concordance was similar for patients with and without cytoreductive therapy, and symptom prevalence was not lower in those who received cytoreductive therapy. No trend towards better physician symptom recognition over time was recorded. Of note, the presence of any symptom (physician-rated) and any severe symptom (patient-reported) at baseline was associated with a higher hazard of death in multivariable models adjusted for age, sex, and disease duration (adj. HR = 1.6 (CI: 1.3, 1.9), p < 0.001 and adj. HR = 1.5 (CI: 1.2, 1.9), p < 0.001, respectively). Among the six symptoms, severe fatigue at baseline and severe weight loss at baseline were both associated with increased hazard of death, with adj. HR = 1.8 (CI: 1.4, 2.3), p < 0.001 and adj. HR = 3.5 (CI: 2.4, 5.0), p < 0.001, respectively. Symptom persistence in general did not result in an increased hazard of death, while, specifically, persistent weight loss led to a higher chance of a fatal outcome (adj. HR = 6.3 (CI: 2.3, 17.0), p < 0.001). Taken together, this analysis on > 3900 MPN patients reports on significant discrepancies in symptom recognition using an intra-individual assessment between patient-reported and physician-reported data. Physicians reported symptom less frequent compared to patients. Physician- and patient-reported symptoms were an independent risk factor for short-term death and should therefore be carefully assessed in clinical routine.