The analysis, which included nearly 4,000 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, 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,” Dr. Visram said 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 Dr. 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.
Dr. Visram and colleagues launched the current study to better understand the potential differences between real-world and clinical trial outcomes. In the analysis, the researchers compared real-world outcomes among patients receiving seven standard multiple myeloma regimens covered by Ontario’s public health plan with patient outcomes reported in phase 3 randomized controlled trials.
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, Dr. 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, Dr. Visram explained.
The only regimen with comparable outcomes in the clinical trial and real-world settings was pomalidomide and dexamethasone, she said. 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.
The study also found that adverse effects were similar between the clinical and real-world groups.
The next step, Dr. Visram said, would be to explore what’s driving the differences in outcomes.
Are patients in the real-world setting older or frailer? Do they have more advanced disease? Are providers using these regimens differently?
Mikkael A. Sekeres, MD, MS, explained that the difference likely comes down to the health of the patient.
Patients in these types of clinical trials “are just these pristine specimens of human beings except for the cancer that’s being treated,” Dr. Sekeres, of the Sylvester Comprehensive Cancer Center at the University of Miami, Florida, said in an earlier ASH press briefing.
Cynthia E. Dunbar, MD, noted that patients in clinical trials have other advantages as well.
“Patients who are able to enroll in clinical trials are more likely to be able to show up at the treatment center at the right time and for every dose, have transportation, and afford drugs to prevent side effects,” said Dr. Dunbar, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute and secretary of ASH. These patients also “might stay on the drug for longer, or they have nurses who are always encouraging them on how to make it through a toxicity.”
Dr. Dunbar 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.”
No study funding was reported. Dr. Visram reported consulting and honoraria relationships with Apotex, Janssen, and Sanofi. Other study authors reported multiple relationships with industry. Disclosures for Dr. Dunbar and Dr. Sekeres were unavailable.
A version of this article appeared on Medscape.com.
