In recent years, the field of hematologic malignancies has advanced at an unprecedented pace, with a steady emergence of novel therapies. While prolonging survival remains a central goal, patients’ quality of life has increasingly become a core dimension in evaluating the true value of treatment. In an interview with Hematology Frontier, Professor Fabio Efficace, Chair of the Health Outcomes Research Unit and Data Center of the Italian Group for Adult Hematologic Diseases (GIMEMA), emphasized that the research paradigm in modern hematology is undergoing a profound transformation.
“Beyond traditional survival endpoints, we must pay much greater attention to health-related quality of life and symptom burden from the patient’s perspective,” Professor Efficace noted. “Patient-reported outcomes (PROs) are a key instrument for realizing truly patient-centered care.” He stressed that PRO data offer a direct and authentic reflection of how disease and treatment affect patients’ daily lives—insights that cannot be fully captured by laboratory parameters or physician assessments alone.
PRO research has now moved well beyond its initial exploratory phase and is increasingly being integrated into prognostic assessment, disease burden evaluation, and even clinical decision-making. This article systematically reviews six major studies presented by Professor Efficace’s team at ASH, highlighting the critical role of PROs in understanding the full impact of hematologic diseases and shaping future directions for research and clinical practice.
PRO Characteristics and Burden in Rare and Myeloid Diseases
VEXAS Syndrome: A Burden Beyond Myelodysplastic Syndromes
Professor Efficace first introduced a pioneering study on VEXAS syndrome, a newly identified rare disease. “VEXAS syndrome presents with complex clinical manifestations and often coexists with myelodysplastic syndromes (MDS), yet the true patient-reported burden had remained largely unknown,” he explained. “Our study was the first to quantify this burden using PRO instruments.”
The study included 59 Italian patients with VEXAS syndrome, who were compared with patients with MDS using propensity score matching. The results were striking. Compared with MDS patients, those with VEXAS syndrome experienced clinically meaningful and significantly worse physical, role, and social functioning, along with more severe fatigue and pain. Professor Efficace highlighted that 66.1%, 62.7%, and 64.4% of patients reported muscle pain, joint pain, and skin problems, respectively, underscoring the distinctive systemic symptom profile of VEXAS syndrome.
Notably, no significant differences in PROs were observed between patients receiving active treatment and those untreated. “This is concerning,” Professor Efficace remarked, “as it suggests that current therapeutic strategies may be insufficient in improving patients’ lived experiences, and that more effective interventions are urgently needed.”
Higher-Risk MDS: The Impact of Socioeconomic Inequalities on HRQoL
Professor Efficace then turned to a frequently overlooked issue in higher-risk MDS: the influence of socioeconomic status (SES) on health-related quality of life (HRQoL). He discussed findings from a large study involving 504 newly diagnosed higher-risk MDS patients, which demonstrated that SES is a strong independent predictor of HRQoL.
Patients with lower SES consistently reported a higher prevalence of clinically significant problems. Severe fatigue was reported by 59.1% of low-SES patients compared with 39.3% in the high-SES group; pain by 53% versus 27.1%; and dyspnea by 74.2% versus 57.6%. Even after adjusting for age, comorbidities, and other confounders, low SES remained an independent risk factor for pain, dyspnea, and impaired cognitive functioning.
“These findings have important public health implications,” Professor Efficace emphasized. “They clearly show that socioeconomically disadvantaged patients with higher-risk MDS bear a disproportionately heavy disease burden and require greater attention and supportive care to address health inequities.”
The Central Role of PROs in Prognostic Assessment and Treatment Evaluation
Relapsed/Refractory Multiple Myeloma: Physical Function Outperforms Traditional Frailty Indices
When discussing the prognostic value of PROs, Professor Efficace highlighted a prospective study in relapsed/refractory multiple myeloma (RRMM) that evaluated the applicability of the International Myeloma Working Group Frailty Index (IMWG-FI) and explored the added value of PROs. The IMWG-FI successfully stratified patients into “fit/intermediate” and “frail” groups with significantly different survival outcomes, with median overall survival of 38 months versus 33 months, respectively.
However, the most notable findings emerged from the PRO analyses. Using bootstrap resampling methods, the study showed that patient-reported physical functioning (PF) was among the strongest predictors of overall survival, with a selection frequency of 90%. In multivariable models, PF remained an independent prognostic factor beyond the IMWG-FI. For every 10-point decrease in the EORTC QLQ-C30 PF score, the risk of death increased by 7%.
Importantly, adding PF to a model containing only the IMWG-FI significantly improved predictive accuracy, increasing the C-index from 0.56 to 0.61. “This suggests that simple patient-reported measures, such as the ability to perform daily activities, may reflect overall health status more sensitively than complex clinical assessments,” Professor Efficace concluded, noting the potential for developing simplified, patient-centered frailty tools that integrate PROs.
CAR T-Cell Therapy in Lymphoma: Baseline Fatigue as an Independent Prognostic Marker
In the context of CAR T-cell therapy, Professor Efficace’s team provided critical evidence from a PRO perspective. In a study of 169 patients with aggressive B-cell lymphomas treated with CAR T cells, the investigators examined the prognostic significance of baseline fatigue prior to infusion.
“Our analyses clearly demonstrated that patient-reported fatigue at baseline, measured using the FACIT-F scale, was an independent predictor of overall survival,” Professor Efficace explained. After adjusting for age, sex, and other clinical variables, each 3-point increase in the FACIT-F score—representing a clinically meaningful improvement—was associated with a 14% reduction in mortality risk. Patients stratified by median fatigue level showed a marked difference in estimated 12-month overall survival (87% versus 73%).
Moreover, patients with higher fatigue reported significantly worse HRQoL across multiple domains at baseline. “This finding underscores that treatment decisions for CAR T-cell therapy should not rely solely on tumor burden or laboratory data,” Professor Efficace noted. “A simple patient-reported measure such as fatigue can help identify particularly vulnerable patients who may benefit from early, intensified supportive care.”
CAR T-Cell Therapy in Lymphoma: HRQoL Trajectories and Recovery Patterns
Beyond prognostic prediction, Professor Efficace’s team also characterized the longitudinal HRQoL trajectories of patients undergoing CAR T-cell therapy. In a prospective study with up to 12 months of follow-up in 170 patients, a clear pattern emerged.
“One month after CAR T infusion represents the nadir of HRQoL,” Professor Efficace explained, particularly in physical functioning, role functioning, and fatigue, all of which showed clinically meaningful declines. Cognitive functioning, however, remained stable throughout the observation period. After the first month, most HRQoL domains demonstrated sustained and clinically significant improvement, continuing through month 12, with the most pronounced gains seen in role functioning and fatigue.
Exploratory analyses further showed that patients who achieved a response by three months experienced substantially greater early HRQoL improvements between months 1 and 3 compared with non-responders. For example, 71.8% of responders experienced clinically meaningful improvement in physical functioning, compared with 28.6% of non-responders. This study was the first to comprehensively depict both the short-term impact and long-term benefits of CAR T-cell therapy on quality of life in a real-world setting, providing valuable data for patient counseling and expectation management.
Methodological Quality and Future Directions of PRO Research
PRO Reporting in Lymphoma and Myeloma RCTs: Substantial Room for Improvement
Finally, Professor Efficace addressed the methodological quality of PRO research itself. He described a systematic analysis of 83 randomized controlled trials in multiple myeloma and lymphoma published between 2015 and 2025, which evaluated PRO reporting quality using the CONSORT-PRO framework.
“The results were far from reassuring,” he stated. Overall PRO reporting quality was highly variable, with a median CONSORT-PRO score of only 9.5 out of a possible 14 or 15. Although most trials reported PRO results across domains, critical methodological details were frequently missing. Only 16% of trials prespecified PRO hypotheses, 33% described PRO data collection methods, and 47% explained how missing data were handled.
One encouraging finding was that 59% of trials published PRO results in separate, dedicated papers following the primary publication, and this practice was associated with significantly higher reporting quality. However, these PRO publications appeared a median of 1.8 years after the main trial report, limiting the timely integration of PRO data into clinical practice. Professor Efficace called for concerted efforts to improve the design, conduct, and reporting of PROs in RCTs and to accelerate dissemination of results.
Summary
Reflecting on these six studies, Professor Fabio Efficace concluded that PROs are indispensable in contemporary hematology research and clinical care. From uncovering the unique and severe burden of emerging rare diseases such as VEXAS syndrome, to revealing the profound impact of socioeconomic inequalities in MDS, PROs offer perspectives that cannot be obtained through traditional clinical measures alone.
More importantly, in prognostic assessment—whether in RRMM or in patients receiving CAR T-cell therapy—simple PRO measures such as physical functioning and fatigue consistently demonstrated predictive value that complements or even surpasses conventional tools. Longitudinal studies of HRQoL trajectories further illustrate how novel therapies affect patients’ lives in real terms, helping clinicians and patients form realistic expectations.
At the same time, the systematic review of RCTs highlights substantial shortcomings in PRO reporting quality, signaling an urgent need for methodological improvement. Looking ahead, Professor Efficace expressed strong confidence that the routine and systematic integration of PROs into clinical pathways and research design will be a key driver in advancing patient-centered care and ultimately achieving the dual goals of improving both the length and quality of survival. Achieving this vision, he emphasized, will require the joint efforts of researchers, clinicians, policymakers, and patient advocacy groups.
Selected Research Abstracts by Professor Efficace’s Team
Abstract 2685 Health-related quality of life and symptom burden of patients with VEXAS: Real-world data from a multicenter observational study
Abstract 138 The prognostic value for survival of frailty and patient-reported outcomes in relapsed/refractory multiple myeloma
Abstract 4408 Quality and timing of patient-reported outcome reports in randomized controlled trials of lymphoid malignancies
Abstract 6389 Socioeconomic inequalities and health-related quality of life in patients with higher-risk myelodysplastic syndromes
Abstract 6278 The prognostic value of patient-reported fatigue for survival in aggressive B-cell lymphomas treated with CAR T-cell therapy
Abstract 6279 Health-related quality of life trajectories in patients with aggressive B-cell lymphomas treated with CAR T-cell therapy
