Health-Related Quality of Life of Patients with Philadelphia-Negative Myeloproliferative Neoplasms Compared with the General Population: A Preliminary Report from the Gimema Prophecy Study

Background The Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). Health-related quality of life (HRQoL) of these patients may be impaired due to the nature of the disease itself as well as by associated treatments.

Purpose We compared HRQoL profile of Italian patients with MPNs, overall and by disease group (ie., PV, ET and MF), with their respective peers in the general population.

Methods Baseline data from an ongoing multicenter prospective cohort GIMEMA observational study (PROPHECY) were analyzed. Adult patients with newly diagnosed MPN with any known IPSS/DIPSS/HIGH-LOW stratification risk score and an initial diagnosis within one year prior to study inclusion were eligible. At study entry, patients completed a battery of patient-reported outcome (PRO) measures including the EORTC QLQ-C30. This questionnaire consists of five functioning scales: physical (PF), role (RF), emotional (EF), cognitive (CF) and social (SF); three symptom scales: fatigue (FA), nausea/vomiting (NV) and pain (PA); six single item scales: dyspnea (DY), sleep disturbance (SL), appetite loss (AP), constipation (CO), diarrhea (DI) and financial impact (FI); and the global health status QoL scale (GHS). HRQoL mean scores of patients with MPNs were compared with that of their Italian peers from the general population (Pilz et al. BMC Public Health 2022;22:1040) and analyses were adjusted by sex, age and health condition. Linear regression models were used to estimate predicted HRQoL scores to comparing to the observed values of the MPN patients. Clinical significance of HRQoL differences between groups (patients vs general population) was determined based on predefined thresholds (Cocks K, et al., J Clin Oncol 29:89-96, 2011). The study was approved from all ethical committee of participating centers and all patients provided informed consent.

Results. Overall, 325 patients with MPN were enrolled in 26 Italian centers from June 2020 to June 2022 and were considered in the current analysis. The median age was 66 years (range 19-90). Of the 325 patients enrolled there, 124, 112 and 89 diagnosed with ET, PV and MF respectively.

Transfusion dependency was present in 8%, 2.5%, and 1% of patients with MF, PV and ET patients, respectively. ECOG/WHO performance status was ≥1 in 26%, 9% and 5% of MF, ET and PV patients, respectively. Splenomegaly ≥5 cm was detected in 21% of MF patients. Platelet count at baseline was higher in ET (median 591 x10^9/L) compared to PV and MF patients (457 and 460 x10^9/L); hematocrit was higher in PV (median 47%) compared to ET and MF patients (43 and 40%). The overall group of patients with MPNs reported clinically relevant worse mean scores compared to general population in 9 out of the 14 EORTC QLQ-C30 evaluable scales for this analysis. Patients with MF patients tended to report larger magnitude of HRQoL differences with general population compared to the ones observed for patients with ET and PV. In particular, medium clinically relevant differences were detected for: role (Δ= 22.6; 95% C.I.= 16-29), cognitive (Δ=12.3; 95% C.I.= 7.2,17), social (Δ=12.9; 95% C.I.= 7.4,18) functioning scales, as well as for the global QoL scale (Δ=12.6; 95% C.I.= 6.3,19). With regard to symptoms, medium clinically relevant differences compared to general population were found for: fatigue (Δ=-17.8; 95% C.I.= -24,-12), dyspnea (Δ=-9.2; 95% C.I.= -15,-3.3), insomnia (Δ=-19.9; 95% C.I.= -26,-12) and diarrhea (Δ=-7.4; 95% C.I.= -11,-3.7). A number of clinically relevant differences were also observed for patients with ET and PV, although in a lower number of EORTC QLQ-C30 scales compared to that found for patients with MF. In any case, both groups (PV and ET) reported a medium clinically meaningful score with regard to SL in comparison with the general population. Details are reported in Table 1.

Conclusions Our findings suggest that Italian patients with MPNs report a clinically relevant worse HRQoL profile across important functional and symptom domains compared with their peers from the general population. Patients with MF seem to report HRQoL impairments across a larger number of HRQoL domains, and of greater magnitude, than that observed for patients with ET and PV. Further analyses are needed to confirm current results and to identify factors associated with HRQoL impairments.

Palandri:AOP: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Kartos/Telios: Consultancy, Honoraria; CTI: Consultancy, Honoraria; Sobi: Consultancy, Honoraria; Sierra Oncology: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Loscocco:Novartis: Speakers Bureau. Iurlo:Novartis, BMS, Celgene, Incyte, Pfizer: Honoraria. Abruzzese:BMS, Incyte, Novartis, Pfizer: Consultancy. Marchetti:GILEAD srl: Honoraria. Luppi:Gilead sci: Other: Travel grant; Abbvie, Jazz Pharma, Gilead sci, MSD, Novartis, Sanofi, Daiichi-Sankyo, Grifols: Membership on an entity's Board of Directors or advisory committees. Pane:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte, BMS, Janssen, Amgen, Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Speakers Bureau. Siragusa:Csl Behring, Takeda, Amgen, Novartis, Bayer, Sobi, Novo Nordisk: Honoraria. Vignetti:IQVIA, Dephaforum, AbbVie, Astrazeneca: Speakers Bureau. Vannucchi:Abbvie: Membership on an entity's Board of Directors or advisory committees; AOP Orphans Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; BluePrint: Membership on an entity's Board of Directors or advisory committees, Other: NA; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees, Other: NA; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Efficace:Amgen: Research Funding; Novartis: Consultancy, Research Funding; Janssen: Consultancy; Abbvie: Consultancy, Research Funding.