A groundbreaking study published in the European Journal of Haematology has revealed that patient-reported physical function before treatment initiation can significantly predict survival outcomes and treatment efficacy in multiple myeloma patients receiving daratumumab therapy.
The research, which pooled data from three major randomized controlled clinical trials—MAIA, POLLUX, and CASTOR—analyzed 1,804 participants with a median age of 66. Approximately half received daratumumab-inclusive regimens, while the remainder were treated with therapies that did not include the monoclonal antibody.
Patient Reports Outperform Physician Assessments
The study found that patients' self-reported physical function assessments before treatment provided more accurate prognostic information than the widely used Eastern Cooperative Oncology Group Performance Status (ECOG-PS) scale, which relies on physician evaluation.
"Patients deemed 'fully active' by ECOG often disclosed substantial physical impairments in their self-assessments," noted lead author Dr. Ahmad Abuhelwa, highlighting a critical disconnect between clinician perceptions and patient experiences.
This finding challenges the current reliance on physician-centered evaluations and suggests that incorporating patient voices into treatment planning could significantly improve outcome predictions and treatment selection.
Differential Benefits Based on Physical Function
The most striking discovery was the relationship between baseline physical function and daratumumab efficacy. Patients reporting lower physical function before treatment derived substantially greater survival benefits from daratumumab therapy compared to those with higher self-reported physical function.
Specifically, patients with lower physical function experienced:
- 47% reduction in all-cause mortality risk (hazard ratio 0.53)
- 66% lower risk of disease progression (hazard ratio 0.34)
In contrast, physically robust patients showed a more modest benefit from daratumumab, with only a 14% reduction in death risk (not statistically significant) and a 47% reduction in cancer progression risk.
Importantly, daratumumab was not associated with increased serious adverse events even in patients with diminished physical performance, alleviating concerns about treatment tolerability in vulnerable populations.
Implications for Clinical Practice
Dr. Ashley Hopkins, a co-author of the study, emphasized the importance of these findings: "This is a critical reminder to clinicians to listen carefully to their patients' functional status before starting therapy."
The research suggests that integrating patient-reported outcomes (PROs) like physical function into routine clinical workflows could substantially enhance predictive accuracy for survival and treatment response. This approach offers a low-cost, pragmatic strategy particularly valuable in assessing older or frail multiple myeloma patients, who face elevated risks of therapy-related toxicity and disease progression.
Global Burden and Collaborative Research
The significance of these findings is amplified by the growing global burden of multiple myeloma. Projections indicate a 71% increase in incidence and 79% rise in mortality by 2045. In the United States alone, over 36,000 new cases and more than 12,000 deaths are anticipated by 2025.
The study represents a collaborative effort between research institutions in the United States, Australia, and the United Arab Emirates, including the H. Lee Moffitt Cancer Center, Flinders University, the University of North Carolina, and Burjeel Cancer Institute.
Toward Personalized Treatment Approaches
Professor Humaid Al-Shamsi, another co-author, highlighted how these findings support a move toward more compassionate, individualized cancer care, particularly for older or physically vulnerable populations.
By identifying patient-reported physical function as a potent biomarker that can refine prognosis and tailor daratumumab therapy, this research challenges oncologists to rethink treatment algorithms and embrace a more patient-centered approach.
Future Directions
Despite the compelling results, the study authors emphasize the need for further prospective research to validate these findings and evaluate whether patient-reported physical function can predict responses to other emerging multiple myeloma therapies.
They advocate for widespread adoption of patient-reported outcomes in both clinical trials and standard oncology practice, which may catalyze a more responsive and adaptable treatment landscape.
As multiple myeloma treatment continues to evolve with therapies like daratumumab, bortezomib, and lenalidomide improving outcomes, this study underscores that optimizing treatment strategies requires a holistic approach that meaningfully incorporates patients' perspectives and experiences.
