General Updates | The longest reported survival to date in any unselected group of patients with multiple myeloma

We were interested in learning whether our approach to myeloma would lead to excellent outcomes, and it does not include what was really until recently the conventional treatment for myeloma, which was induction therapy followed by a stem cell transplant. And in this study, number one, we did not transplant any patient in the frontline setting, and only one patient was transplanted in the second-line setting. Second, we wanted to learn outcomes in unselected patients because patients who are usually reported on are part of clinical trials and they’re selected in such a manner that they’re usually in better shape than the average patient. In this case, we only used patients who were started on treatment in our center as well because we didn’t want to bias the data by using patients who’d gotten treatment elsewhere and then happened to come to our center, say, five or 10 years after diagnosis, and we didn’t think it was appropriate that we take credit for outcomes that we were really not part of. In addition, many studies done at larger centers include patients that have to be well enough and wealthy enough to get to the center, and so obviously that isn’t really an unselected patient. So we felt this would be an unbiased group. 

So even though we had over 1,000 patients, we only included the 175 who initiated therapy in our clinic, and this included the period about 2005 to 2024. Now, these patients were largely treated up front with a regimen that we like a lot, which includes doxorubicin, a form of chemotherapy called an anthracycline, Velcade, which is a proteasome inhibitor, and steroids, usually dexamethasone, although many of these patients transitioned to maintenance therapy without the doxorubicin and included Velcade, dexamethasone, and Medrol. There were some patients with a more aggressive disease in which we included Revlimid. This study was really done during a time in which CAR T-cells and bispecific antibodies were not part of the treatment regimens that we were giving patients, so none of those patients received that treatment. 

What was impressive was the survival, which approached an average of 13 years among a group of patients who were unselected, none of whom had upfront transplant and were treated fairly unconventionally upfront with doxorubicin. And we were really happy to see that. We also learned that although there’s a lot of emphasis on having a complete remission or inability to measure the myeloma, that that didn’t really predict overall survival. It did, in fact, predict the time the disease is going to come back, which is obvious to me because if you can’t measure it, you’re going to have a longer remission among those who are not in complete remission in which you can measure the marker and therefore you can see it go up. We now know that’s probably true with more recent work using more sensitive assays in which you can measure the monoclonal protein, the myeloma marker, at a much lower level than using conventional techniques. And we know these patients are really progressing within months, not years, and I think that’s an important finding as we think about really what a complete remission means in myeloma. 

Well, I think the key takeaways are number one is that you really have to think about myeloma now more as a chronic disease, thankfully, given this data. And therefore, a lot of things we didn’t used to care about when I started my journey with myeloma in the 80s, such as routine care – mammograms, colonoscopies, monitoring the heart – it wasn’t as big a deal. But now people are living decades, they better worry about these other things, because they may come into play as patients are living many, many years, not just a couple of years. That’s, I think, an important part of this. Secondly, I do believe that we have to focus on what my good friend Gio on our board at the Institute said to my wife many times when she was on stage at his theater. It’s not about more, it’s about being more specific. That has several implications. One is be specific to the patient’s needs and also try to knock out the myeloma and not the rest of the patient. Many of our treatments, I believe, are overly aggressive, leading to many side effects that impact quality of life, and if your quality of life is worse, you’re going to have a worse survival. So I think we have to think about myeloma as a marathon. It’s a 26-mile race, so let’s pace it and not do sprint racing and drop out in the first few miles by running fast but not getting the whole race done. 

Another major point would be the results of clinical trials done in centers outside the United States may not necessarily follow the results in a clinic like mine because the options may be markedly limited there compared to what I can give patients. And so, therefore, randomized trials looking at A and B versus C and D may not be necessarily the same findings in terms of what I care about and patients care most about, and that is how long they’re going to live and with what quality of life. They may not be relevant to a sophisticated clinic in a U.S.-based center. One has to be very careful about interpreting these kind of results. And I think you have to be also very careful about using too much treatment and too expensive treatment that doesn’t necessarily result in better outcomes. And as I said a few seconds ago, the only thing patients care about is how long am I gonna live, doctor, and with what quality of life? And I think that’s the thing we have to remember as we care for myeloma patients.

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