Comparison of the efficacy in clinical trials versus effectiveness in the real-world of treatments for multiple myeloma: A population-based cohort study.
In the real world, outcomes for patients with multiple myeloma who received standard regimens were dramatically worse than those reported in clinical trials, a new study found
The analysis, which included nearly 4000 patients with multiple myeloma, revealed that patients in a real-world setting demonstrated worse progression-free and overall survival on six of seven standard treatments compared with patients evaluated in randomized controlled trials.
Lead author Alissa Visram, MD, MPH, who spoke about the study at the annual meeting of the American Society of Hematology (ASH), said the findings will likely change the way she speaks to patients about their potential outcomes. "I'll probably present both numbers [from real-life and clinical-trial data] and give them a sense of the best-case scenario," said Visram during an ASH media briefing. But she said she will also caution her patients that the real-world numbers reflect how people on these drugs actually fare.
The effectiveness of multiple myeloma drugs remains unclear outside the clinical trial setting, explained Visram, of the Division of Hematology at the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. Outcomes from randomized controlled trials form the basis of drug approvals but many patients in the real world do not meet the "stringent" trial inclusion criteria.
The retrospective study included 3951 patients with newly diagnosed and refractory multiple myeloma treated from 2007 to 2020 in Ontario. Regimens for newly diagnosed transplant ineligible patients included lenalidomide plus dexamethasone and triple therapy with bortezomib, lenalidomide, and dexamethasone. Regimens for patients with relapsed disease included pomalidomide plus dexamethasone or carfilzomib plus dexamethasone as well as triple combinations including carfilzomib, lenalidomide, and dexamethasone.
Overall, Visram and colleagues found that patients in the real-world setting demonstrated worse overall survival for six of the seven regimens evaluated (pooled hazard ratio [HR], 1.75; P = .010). The real-world patients also had worse progression-free survival for six of the seven regimens (pooled HR, 1.44; P = .034).
For these regimens, progression-free survival was at least 3-18 months longer in the clinical trial cohort, while median overall survival was at least 19 months longer compared with real-world patients.
The only regimen with comparable outcomes in the clinical trial and real-world settings was pomalidomide and dexamethasone. One reason could be that patients receiving pomalidomide plus dexamethasone in the clinical trial setting had similar or more advanced disease than those in the real-world setting.
Mikkael A. Sekeres, MD, MS, of the Sylvester Comprehensive Cancer Center at the University of Miami, Miami, Florida, explained that the difference likely comes down to the health of the patient.
Cynthia E. Dunbar, MD chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute and secretary of ASH, said hematologists and patients should consider randomized controlled trials to be "the best possible outcome, and perhaps adjust their thinking if an individual patient is older, sicker, or less able to follow a regimen exactly".
See-"Comparison of the Efficacy in Clinical Trials Versus Effectiveness in the Real-World of Treatments for Multiple Myeloma: A Population-Based Cohort Study"- ASH Program: Oral and Poster Abstracts. Type: Oral. Session: 905. Outcomes Research – Lymphoid Malignancies: Outcomes Research in Myeloma: What's New? Hematology Disease Topics & Pathways.
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