Multiple myeloma regimens significantly less effective in real-world treatment settings
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Key takeaways:
- Patients treated in real-world settings had significantly worse survival outcomes for six of seven regimens evaluated.
- All regimens exhibited comparable safety, regardless of the treatment setting.
SAN DIEGO — Standard care treatments for multiple myeloma conferred markedly shorter survival benefits in real-world settings, study results presented at ASH Annual Meeting and Exposition showed.
Data from a retrospective analysis revealed that six of seven standard care regimens evaluated had significantly shorter PFS and OS in real-world clinical practice compared with their performance in registrational phase 3 randomized controlled trials.
Despite this drop in efficacy, the standard care regimens evaluated performed similarly in terms of safety under both real-world and clinical trial conditions, according to study investigators.
“The results of this study highlight a significant efficacy-effectiveness gap with multiple standard-of-care regimens for treatment of multiple myeloma,” Alissa Visram, MD, MPH, a hematologist at The Ottawa Hospital Research Institute, said during a press briefing. “This underscores the importance of real-world data to understand whether randomized controlled trial outcomes are generalizable to our patient population.”
Background
New treatment regimens are elevated to standard care status through their superior performance against existing therapies in randomized phase 3 clinical trials. The shortcoming of this process is the clinical trial patient population, which often does not reflect the diversity of patients treated in real-world settings due to sponsors’ typically stringent selection criteria.
Results from these trials are often used in developing evidence-based practice guidelines and what clinicians use to counsel their patients about the benefits of a particular treatment, according to Visram.
“We know that efficacy outcomes in the ideal clinical trial setting are often better than the effectiveness in patients in the real-world setting,” she added.
The result is an “efficacy-effectiveness gap,” Visram said, referring to the difference between a treatment’s maximum achievable response during clinical trials and how well that same treatment works for its task of eliminating malignant cells under real-life conditions.
“What we don’t know is how much does randomized clinical trial efficacy differ from real-world effectiveness for multiple myeloma therapies,” she said. “That’s exactly the question we hope to answer in this study.”
Methodology
Visram and colleagues performed a retrospective population-based study to evaluate the efficacy of standard care regimens for multiple myeloma in registrational randomized controlled trials compared with their effectiveness in real-world clinical practice.
The analysis used patient clinical data from a database maintained by a publicly funded health care system in Ontario, Canada. The real-world study cohort included 3,951 adults with multiple myeloma treated between January 2007 and December 2020 using seven standard-care regimens eligible for public insurance reimbursement based on results of previous registrational phase 3 randomized controlled trials.
The investigators calculated Kaplan-Meier survival curves from pivotal phase 3 randomized controlled studies to develop patient-level estimates of OS and PFS. They also conducted meta-analyses to determine the difference in PFS and OS outcomes between real-world patients and those treated during clinical trials, with HRs providing effect estimates.
Differences in PFS, OS and serious treatment-related adverse events served as the study’s primary outcome measurements.
Key findings
Results of the meta-analysis showed that patients with multiple myeloma treated as part of real-world clinical practice had significantly shorter median PFS compared with those treated during randomized controlled trials for six of seven regimens evaluated in the study (pooled HR = 1.44; 95% CI, 1.34-1.54).
Likewise, patients treated in real-world settings experienced worse OS compared with those treated during randomized controlled trials for six of seven regimens in the analysis (pooled HR = 1.75; 95% CI, 1.63-1.88).
Only one of the regimens — pomalidomide plus dexamethasone for patients with relapsed or refractory disease — performed better in the real-world setting than it did during its phase 3 randomized trial.
Safety results revealed comparable frequency of serious treatment-related adverse events for all seven of the regimens included in the study.
Clinical implications
Real-world studies are poised to become increasingly important for driving decision making about treatments for policy makers, physicians and patients, especially given the emergence of targeted and immunotherapies with significant toxicities and financial burdens, according to Visram.
Her approach to clinical practice will likely change because of the study, as Visram said she plans to present both real-world and clinical trial data to patients to illustrate the potential variability in treatment outcomes.
“Often in multiple myeloma, there are options as to which treatment a patient can receive at the next line of therapy,” she told Healio. “Data from studies like ours will enable people to make better treatment choices for themselves.”
Perspective
Back to TopCynthia E. Dunbar, MD
Entry criteria for clinical trials is part of this. Kidney function, blood counts and other factors we use as cutoffs for clinical trials may not always apply to patients we’re treating in the real world. Also, patients who are able to enroll in clinical trials are more likely to be able to show up at treatment centers at the right time for every dose, they have transportation, they may be in a higher socioeconomic class so they can afford drugs to prevent side effects — which may allow them to stay on treatment for longer — or they may have nurses who are always encouraging them about how to make it through a toxicity.Hematologists and patients clearly should consider randomized controlled trials as the best possible outcome and perhaps adjust their thinking when an individual patient is older, sicker or less able to follow a regimen exactly when they’re deciding how to apply research results to their own practice.
This also shows we need to try to improve access to health care in such a way that we can try to ensure patients in the real world are able to have high-quality care all of the time, like patients in clinical trials usually have.
Perspective
Back to TopJames R. Berenson, MD
In this study, researchers looked at a large group of patients in a registry who received a series of drug combinations for treatment of multiple myeloma. The analysis included data from several thousand patients, and researchers assessed whether results from clinical trials were representative of what happens in the real world. The findings clearly indicate that is not the case with most regimens, with the exception of one — pomalidomide and dexamethasone. The results from the real-world setting showed inferior outcomes in terms of PFS and OS, and responses were similarly lower in the real world.
There are multiple reasons for this. Obviously, patients on clinical trials have to meet certain criteria to be enrolled. They must have a certain level of performance, their labs have to fit and their age has to be appropriate. Therefore, they tend to have better outcomes.
We recently published real-world outcomes about our own patients in Targeted Oncology. They showed a median OS of almost 12 years, which is longer than any reported in the world, despite the fact that we included everybody. So, I think the results also depend on the quality of care that you get at different institutions or in different parts of the world. In general, though, real-world studies do tend to show inferior outcomes compared with clinical trial data.
Reference:
Jew S, et al. Target Oncol. 2023;doi:10.1007/s11523-023-00990-6
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Visram A, et al. Abstract 541. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2023; San Diego.
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