Improving Quality of Life in Multiple Myeloma Through Bortezomib Dose Reduction With Rahul Banerjee, MD, FACP, and Gurbakhash Kaur, MD
At the 2023 American Society of Hematology (ASH) Annual Meeting, Dr. Rahul Banerjee, Editor in Chief of Oncology Data Advisor, sat down with Dr. Gurbakhash Kaur, an Assistant Professor of Medicine at the University of Texas (UT) Southwestern Medical Center, to discuss their abstract about real-world dosing and prescribing patterns of bortezomib in newly diagnosed multiple myeloma. Dr. Banerjee and Dr. Kaur debate the pros and cons of once- versus twice-weekly dosing of bortezomib, its impact on tolerability and outcomes, and changes in trial design that are needed to make once-weekly dosing a new standard in clinical practice.
Oncology Data Advisor: Hi, everyone, welcome to Oncology Data Advisor. Today, we're here at the ASH Annual Meeting, and I'm joined by our Editor in Chief, Dr. Rahul Banerjee, and Dr. Gurbakhash Kaur. Thank you both so much for coming on today.
Gurbakhash Kaur, MD: Thank you for having us.
Rahul Banerjee, MD, FACP: Thank you, Keira. It's exciting to be here in sunny San Diego. I'll be helping Keira to interview Dr. Kaur about her mentee's oral presentation tomorrow, which Dr. Kaur is a senior author on. The study is about real-world observational data surrounding bortezomib in myeloma and how it should be dosed, versus how it is dosed, versus how it will be dosed in the future. With that in mind, Dr. Kaur, Gurbakhash if I may, can you just walk us through a little bit why you wanted to look into this?
Dr. Kaur: So, Rahul, this started about a year ago when the two of us met and we had this deep discussion about the impact that we want to have when it comes to changing practice patterns in myeloma. The two things that we both felt deeply about were how significant the rate of neuropathy is with twice-weekly bortezomib and why it is still being prescribed that way. I think our clinical practice differs a lot, in that we do it in a once-weekly fashion.
Our collaboration began in a very curious fashion to understand what's really happening in the real world. Is this impacting survival? Is it impacting patients' neuropathy and their quality of life? That's how this all started, and here we are a year later with an oral presentation at ASH.
Dr. Banerjee: I completely agree. To add some context for those listening at home, it's tricky because our clinical trials have continued to use twice-weekly bortezomib, which is an injectable drug for myeloma. It's typically dosed on Monday and Thursday. The patients come in twice per week for clinic visits, and as Gurbakhash just said, this means more neuropathy and more time in clinic.
Smaller studies have shown that there's no difference with once-weekly or twice-weekly administration. But because the trials are written with twice-weekly bortezomib, we hypothesized that patients were still getting twice-weekly bortezomib, because that's what the studies did and that's what their doctors were just used to, despite us having changed our practice long ago.
Dr. Kaur: And we see this still in many practices wherein patients are referred to us for stem cell transplant, that they're still getting twice-weekly bortezomib with a significant neuropathy. Alluding to your earlier statement about the clinical trials, clinical trials were being proposed that were presented to us to open other institutions where it's third-line and fourth-line and bortezomib is still being given in a twice-weekly fashion. Honestly, I could not open those trials, so I've said no to them. But I think we needed to have an impact and really study and provide data on this. What is actually happening? Are we seeing differences in progression-free survival (PFS) and survival? How can we change this going forward? Because the twice-weekly bortezomib, I don't strongly believe in that.
Dr. Banerjee: I completely agree. I think in oncology across the board, we always assume that bigger is better when it comes to dosing—more doses, get them in faster and harder into patients. We wanted to find out if that really matters, and we did find out. Can you tell us about what the analysis you did was?
Dr. Kaur: We came together, and we looked at the Flatiron Health Registry, which is a large database that contains patients starting in 2011. We looked at a more modern cohort because we wanted to see what the practice is in a population that's more representative of what we are doing in today's practice.
We had about 2,500 patients and we noted that two-thirds of those patients had higher utilization of once-weekly, versus one-third of that with twice-weekly.
Additionally, we saw that over the past five years from 2018 onwards till now, we had a slow uptick of going from twice-weekly to once-weekly. It was 57%. Last year, it was about 75%. Probably the greatest uptick that we saw was around the pandemic era. That probably influenced a lot of practices to go into once-weekly because we wanted to limit patient exposure and patient visit time to reduce the risk of COVID-19 toxicity. We saw that the utilization of once-weekly increased over time.
Then subsequently, in terms of results, what we saw was that the peripheral neuropathy risk was much higher, about 30%, with twice-weekly versus only 18% with once-weekly. Furthermore, when it came to results, the PFS was very similar between the two groups, and the overall survival was not reached, which is very representative and accurate towards what is happening in real life. Those were some of the data that we highlighted.
Dr. Banerjee: There's so much to unpack there. Maybe we can talk about the prevalence section first, because, as you alluded to, smaller centers have looked at this in older data of maybe 100 or 200 patients. You looked at 2,500 patients, a much larger population and probably more community-based patients as well, not just patients treated at big academic centers.
Dr. Kaur: Yes, 80% of the cohort ended up being community-based in the overall Flatiron Health Database, and our practice had similar trend as well.
Dr. Banerjee: Agreed, agreed. I think the bottom line from that first part is that still in the modern era—up until just a couple of years ago, probably even still today—a quarter of patients in the US are still getting twice-weekly bortezomib, even though nobody is asking them for it. All of us recommend once-weekly bortezomib. Everyone but the clinical trial sponsors and everything but the published old, old trials recommend once-weekly bortezomib. We're just not there yet, and the neuropathy is unfortunate. Have you seen cases of this with your patients? I'm sure you have.
Dr. Kaur: I do. Actually, I think I'm very aggressive about reducing the dose of bortezomib when I do see it in my practice. In my practice, I do only once-weekly, but with the twice-weekly bortezomib, I see similar rates of neuropathy when patients get referred to me. I'm at UT Southwestern in the academic center, so a lot of community physicians refer to us for stem cell transplant, and we see the similar patterns.
Dr. Banerjee: As you alluded to, the overall survival (OS) wasn't reached, and as you'll see in the presentation that Dr. Kaur's mentee is presenting tomorrow, the PFS had completely overlapping curves. So, next week, if you meet you a community oncologist who has started their patient on twice-weekly bortezomib, what do you tell them?
Dr. Kaur: I usually tell them to go back to a once-weekly schedule, but it just depends on where you meet the patient. If I'm meeting them towards the end of induction, it's sort of a done deal, but if I meet them early on, I may advise them of a regimen that's once-weekly. But there's a lot to change when it comes to this practice pattern. There are practice pathways that organizations have when it comes to selecting oncology treatments. Obviously, as you and I have talked about, it's about who your pharmacists are, how closely you are working with them, and whether they are flexible in modifying the drug regimen. There are a lot of layers of complexity here.
Dr. Banerjee: Completely agreed, and I think that it's hard because sometimes the community oncologists are busy, and the pharmacists are busy, and they're just going by the trial. But as you're alluding to, our loyalty is not to the trial design. Our loyalty is to our patients, and I think we can do a better job with it.
I'm excited to see the presentation tomorrow. I'm sure we'll have more podcasts to come about this topic. Hopefully, clinical trials going forward will use once-weekly bortezomib by default, just because that question has now been answered. There may be scenarios that are exceptions, but for everybody else, once-weekly bortezomib is the way to go. Thank you, Dr. Kaur, for your time.
Dr. Kaur: Thank you for having me.
About Dr. Banerjee and Dr. Kaur
Rahul Banerjee, MD, FACP, is an Assistant Professor in the Division of Medical Oncology at the University of Washington, and he also holds a faculty appointment at the Fred Hutchinson Cancer Center. He previously completed his Hematology/Oncology Fellowship and Advanced BMT/CAR-T Fellowship at the University of California, San Francisco. His clinical interests are in multiple myeloma, amyloid light-chain (AL) amyloidosis, and CAR T-cell therapy. His research interests are in toxicity management, digital health, and the patient experience.
Gurbakhash Kaur, MD, is an Assistant Professor of Medicine in the Department of Internal Medicine at the University of Texas Southwestern Medical Center. Dr. Kaur's specialty and research expertise revolve around stem cell transplantation, immunotherapy, CAR T-cell therapy, and multiple myeloma. She actively participates in clinical trials for novel therapeutic options and quality-of-life improvements in treatment of multiple myeloma.
For More Information
Hoff FW, Banerjee R, Khan A, et al (2023). Retrospective observational study on real-world bortezomib prescribing patterns and outcomes in newly diagnosed multiple myeloma. Presented at: 2023 American Society of Hematology Annual Meeting. Abstract 544. Available at: https://ash.confex.com/ash/2023/webprogram/Paper178950.html
Transcript edited for clarity. Any views expressed above are the speakers' own and do not necessarily reflect those of Oncology Data Advisor.