Many of us know of clinical trials, but a less familiar term, real-world data (RWD), can also carry significant weight in supporting Food and Drug Administration (FDA) approval of drugs or changes to recommended drug usage. Real-world data refers to health status or care delivery information for a patient and can come from various sources (e.g., electronic health records, medical claims data, product or disease registries data, and others). The proteosome inhibitor bortezomib is part of the currently used chemotherapy regimen for multiple myeloma with treatment frequency being once- or twice-weekly. The real-world data was particularly useful for evaluating efficacy between these two treatment regimens of bortezomib for multiple myeloma. Specifically, outdated twice-weekly dosing was being used in clinical trials as the standard-of-care despite some clinics implementing once-weekly dosing as standard-of-care. To get to the bottom of this discrepancy and sweep away any cobwebs of less-optimal care recommendations, a study using real-world data was initiated. Dr. Rahul Banerjee, an Assistant Professor in the Clinical Research Division at Fred Hutchinson Cancer Center, teamed up with Dr. Gurbakhash Kaur, an Assistant Professor at the University of Texas Southwestern, to use real-world data to compare the efficacy and safety between once- and twice-weekly treatments of bortezomib for multiple myeloma patients. These findings were published in the Blood Cancer Journal.
The real-world data was collected using Flatiron, a platform that employs AI to collect data from health records. “In our large real-world study of almost 2500 patients, twice-weekly bortezomib was associated with worsened toxicities but virtually identical progression-free survival (not to mention twice as many clinic visits for injections),” shared Dr. Banerjee. These findings highlight that in this situation, one treatment per week is better than two. Furthermore, patients traveling less frequently to the clinic for treatments is not an insignificant benefit. Decreasing clinic visits for patients improves patient quality of life and may reduce exposure to hospital-associated infections. Furthermore, twice-weekly bortezomib causes peripheral neuropathy in ~35% of patients, while once-weekly treatment limits this side effect by almost half to 18.5%. These findings reveal that twice-weekly treatment is unnecessary and should be removed as standard-of-care due to the increased risk of associated side effects.
A globally distributed survey of physicians also uncovered that physicians prefer once-weekly bortezomib treatment. But then why do clinical trials still use twice-weekly bortezomib as standard-of-care? Dr. Banerjee shared his viewpoint, “Because of perceived fears that regulatory agencies will view trials with once-weekly bortezomib to be substandard, many large trials continue to dose bortezomib twice per week (e.g., on Days 1, 4, 8, and 11 of 21-day cycles) based on the drug's dosing schema from over a decade ago. This bizarre dichotomy between how physicians treat patients in real life and how clinical trials continue to operate needs to end. We hope to see a future where once-weekly bortezomib is the norm in multiple myeloma trials. Our study hopefully puts the metaphorical "final nail in the coffin" in this outdated approach.”
With the study completed and advisement of once-weekly bortezomib supported by real-world data, Dr. Banerjee and his colleagues are reaching out to drug companies and to the FDA and advocating for one-weekly dosing to replace twice-weekly. Additionally, Dr. Banerjee shared, “This is a good example of where real-world data is generating answers to questions and helping improve clinical trials down the line! Many of our patients have questions about real-world evidence and what it means, especially when consenting to those repository studies we run.” Therefore, the publication of these findings using real-world data and sharing this information with a general audience will help to inform patients of the real impact that sharing this data can have on improving patient care. To conclude, Dr. Banerjee recognizes the international working group co-led by himself and Dr. Kaur and the mentorship provided by Dr. Vincent Rajkumar, a Professor of Medicine at Mayo Clinic.
Fred Hutch/University of Washington/Seattle Children's Cancer Consortium members Drs. Rahul Banerjee and Andrew Cowan contributed to this work.
Hoff FW, Banerjee R, Khan AM, McCaughan G, Wang B, Wang X, Roose J, Anderson LD Jr, Cowan AJ, Rajkumar SV, Kaur G. 2024. Once-weekly versus twice-weekly bortezomib in newly diagnosed multiple myeloma: a real-world analysis. Blood Cancer J. 14(1):52.