Researchers identified a 75% higher rate of mortality among patients treated for multiple myeloma in real-world hospital settings compared with rates reported in clinical trials involving common therapies. The new findings were presented by Visram et al at the 2023 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 541).
Background
Multiple myeloma is often difficult to diagnose in its earliest stages because it is rare, and symptoms can go unrecognized. As a result, many patients with the disease face poor prognoses even with available treatments.
“The criteria for clinical trial eligibility are often quite stringent, so the results are not always generalizable,” explained lead study author Alissa Visram, MD, MPH, of the Ottawa Hospital Research Institute. “It’s not a surprise that real-world patients don’t do as well as those in clinical trials, but our study is the first to quantify the difference. It suggests we need to change our frame of reference and better contextualize what outcomes we would expect our patients to have.”
Study Methods and Results
In the new study, the researchers compared the mortality, progression-free survival, and severe adverse event rates from phase III clinical trials for seven multiple myeloma treatment regimens with the outcomes of 3,951 patients who received the same treatments in a real-world hospital setting from 2007 to 2020. Among the treatment regimens involved in the study were lenalidomide/dexamethasone and bortezomib plus lenalidomide/dexamethasone for patients with newly diagnosed multiple myeloma who were ineligible for stem cell transplant; and carfilzomib plus lenalidomide/dexamethasone, carfilzomib plus dexamethasone, daratumumab plus lenalidomide/dexamethasone, daratumumab plus bortezomib and dexamethasone, and pomalidomide plus dexamethasone in patients with relapsed multiple myeloma.
The researchers discovered that the patients treated in real-world hospital settings had a 44% higher rate of disease progression or mortality and a 75% higher rate of mortality, on average, compared with the patients who participated in clinical trials. Using hospitalization as a proxy for assessing the rates of severe adverse events among real-world patients, the researchers found comparable rates of severe adverse events among clinical trial participants and real-world patients.
Further, pomalidomide plus dexamethasone was the only treatment regimen that performed as well as or slightly better in the real-world hospital settings than in clinical trials. They hypothesized that this may have been because of the use of this treatment regimen in real-world hospital settings with comparable or slightly fewer exposures to prior therapies.
Conclusions
The researchers emphasized that their new study was not designed to determine the factors contributing to the differences that were observed; however, they noted that several factors may have been responsible. For instance, the real-world patients tended to be older and have more comorbidities than those who participated in clinical trials. Previous research has also demonstrated that real-world patients often have more comorbidities than patients in clinical trials and, therefore, may not tolerate treatments as well as those involved in clinical trials.
In addition, clinical trials are typically carried out in medical centers that see a high volume of patients with rare diseases, where physicians with more experience can administer complex treatment regimens and handle toxicities more efficiently than those in community medical centers where many patients typically receive care. The researchers underscored that patients in historically marginalized communities are often disproportionately excluded from clinical trials and may lack the resources necessary to keep up with clinic visits, which can lead to poorer outcomes. Such factors can widen the gaps between clinical trials and real-world settings in terms of patients’ health status and the care they receive.
“As clinicians, we need to acknowledge that outcomes might not be as good in the real world. [Physicians] often use clinical trial results to explain to patients what to expect with treatment, but it’s important to understand that [they] may be doing more harm if [they] don’t know whether this [clinical trial result] is actually applicable to [their] patients,” revealed Dr. Visram.
Although the new findings were disappointing, the researchers highlighted that they can enhance informed decision-making by providing physicians, regulators, and patients with more accurate expectations of the risks and benefits of cancer therapeutics; and underscore the limitations of clinical trials to predict the outcomes of patient populations that often differ from those in clinical trials in terms of demographics, health status, and care settings such as community practices vs academic medical centers.
The researchers suggested that more diverse participants should be included in clinical trials and that conducting trials in community health centers may lead to results that better reflect what can be expected in the real world. They concluded that further studies may be needed to better understand the factors accounting for the poorer outcomes observed in real-world settings.
Disclosure: For full disclosures of the study authors, visit ash.confex.com.
