Published on July 15, 2020
Myeloma Treatment News: What's Changing?
What's the latest news for myeloma treatments? New myeloma treatments were discussed at the American Society of Clinical Oncology (ASCO) and European Hematology Association (EHA) conferences. Will this new information change the standard of care for myeloma patients?
In this segment from our recent Myeloma Answers Now program, host Andrew Schorr has a conversation with Dr. Luciano Costa from the University of Alabama at Birmingham O’Neal Comprehensive Cancer Center and Dr. Joshua Richter of Tisch Cancer Institute at Mount Sinai. Watch as they discuss results from the ENDURANCE trial, other myeloma clinical trials involving daratumumab and how new treatments are being approved during COVID-19.
This program is sponsored by Janssen Biotech, Inc. This organization has no editorial control. It is produced by Patient Power and Patient Power is solely responsible for the content.
Transcript | Myeloma Treatment News: What's Changing?
And good morning, good afternoon, good evening, wherever you are in the world. I'm Andrew Schorr, near San Diego for Patient Power. Welcome to this myeloma Answers Now program. Thank you to Janssen for being the sponsor, although to be clear, Janssen has no editorial control. We have two noted myeloma experts with us. One joining us from New York City, one joining us from Birmingham, Alabama. In New York at Mount Sinai School of Medicine and The Tisch Cancer Institute there, is Dr. Joshua Richter and also Dr. Luciano Costa, joining us from Birmingham, Alabama. And these are noted myeloma researchers as well as seeing patients. So they do lots of clinical trials, and they're looking at really, how do the latest studies, some that they're involved in, change things or not? And what's happening in the future, that could be a change for you living with myeloma, hopefully on a really long journey and with the highest quality of life.
So that's what it's about, right? And that's what these doctors are dedicated to. Now, there've been some major medical meetings just in the last month or so. The American Society of Clinical Oncology, and then over in Europe, although both virtual, European Hematology Association meetings, studies typically come out. And then these gentlemen are involved in studies all the time, and also monitoring things that the FDA is doing, about when maybe new drugs will be approved, when there'll be a committee meeting to discuss approval, is more research needed. And all of that affects you, the myeloma patient.
I'll start with you, Dr. Richter. We've had more myeloma medicine approvals over the last few years. I mean, it's just mind-blowing and so great for patients. So you've got three-drug combinations, four-drug combinations, you had a new class of medicine approved, and then you have other new things going on. So first of all, there's more hope than ever before, but it's also an alphabet soup. Isn't it?
Yeah. I mean, you've got things and I'll just rattle off some of these acronyms people have. Cell mods, ADCs, bi-specific antibodies, BCMA medicines, combinations with either VRd or KRd. So the first question to you, Dr. Richter is, is there anything out of these medical meetings where you'd say, "Oh my God, we quickly have to do something different for patients.”?
So these meetings, even when they're not virtual, they're just a cacophony of meetings and studies and data altogether. And much of it is about the next generation of drugs. So some of the most exciting stuff at these meetings are about drugs that will probably not be approved for a few years yet. In terms of things that change what we do day-to-day, there was a big study that was presented by the main authors were at the Mayo Clinic, and it was a study called the ENDURANCE trial. And what the ENDURANCE trial did, was look at two very prominent induction regimens, so very prominent regimens that we use for people when they're initially diagnosed with myeloma. One is called VRd, which is a combination of bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (Decadron), which many people listening in may have been on or know quite a bit about.
And then a little bit less commonly used combination of KRd, the combination of carfilzomib (Kyprolis), Revlimid, and dexamethasone. And these two regimens were compared head-to-head to see what ought to be the standard for your average patient coming in to a myeloma clinic. And so the main outcomes of the study were, there doesn't appear to be much of a difference between the two regimens. Velcade, as people may unfortunately know, has a slightly higher risk of neuropathy, numbness and tingling in the fingers and feet. The other regimen with Kyprolis had a higher rate of causing heart and kidney issues. And the conclusions of the authors were that VRd still represents the standard. Now though, the one little caveat is that these tended to be older patients, tended not to go to transplant, and the trial was looking at people with standard-risk cytogenetics, not high-risk cytogenetics. So although there still may be a role for KRd in younger patients with higher risk disease, this really cemented in our minds that generally speaking, VRd should be the standard.
Okay. Dr. Costa, do you agree with that?
I agree totally. I think the perhaps less emphasized measurements of this trial is at the end of the day, it's going to be the studying of newly diagnosed myeloma. It's very challenging to do clinical trials because the majority of the patients, fortunately, do very well for very long with a combination of three drugs. So I think the lesson learned from this study is, we're not going to make much of a headway by substituting one drug by another one of the same class. We need much greater differences to really move the needle. And that seems, in my opinion, I think the data is now very robust, that is really with a combination of monoclonal antibodies.
So we have seen now in all three clinical trials combining daratumumab (Darzalex), the C38 monoclonal antibody with other backbone myeloma regimens, and in all those trials, daratumumab improved the progression-free survival. In at least one of those trials also improved the overall survival. It seems it can be a little bit challenging to change practice because it's one more drug that adds toxicity. But I think that has really led to a significant improvement. And one thing that we had a chance to show both at ASCO and EHA there was some concern early on that some of those trials of patients with newly diagnosed myeloma did not show an advantage for adding a monoclonal antibody to patients with high-risk cytogenetics. And we were wondering if that was really a biological thing, and those patients were just don't respond to daratumumab, or it was much a matter of trial design and under-representation of those patients, so even though those patients may be about a quarter of the myeloma patients when you go into clinical trials, they're only about 10, 15% for various reasons.
So we did what's called a meta-analysis, which is essentially combining data from multiple studies to answer a more narrow question. And that showed clearly that patients with high-risk cytogenetics also benefit from adding daratumumab to their initial regimen. And I think that is really important because we can extend the benefit that is being seen across those trials to also that subset of patients.
Okay, let's mention, by the way, there've been various FDA approvals, and one of them was on a quicker injection if you will, of daratumumab, so that may help people where that drug is added. So it's minutes rather than hours. Let's face it guys, we're talking about this during the COVID pandemic. So Dr. Richter there in New York - New Yorkers came together and truly flattened the curve, so congratulations to you. But in Birmingham, Alabama, not so much right now. And you're worried about it going up. And myeloma patients anywhere say, "Well, gee, you guys are talking about infused therapies. Yes, they're oral therapies, or I may need blood tests, or I might need immunoglobulin injected or things like that." So let's just talk about all of this and in safety. So Dr. Richter, you guys have figured it out in New York, right. That people can have the myeloma treatment they need, including infused therapies and you can protect their safety, right?
Yeah. I don't know that we've figured out anything that hasn't, I think it's a chronologic shift that we just got there a little bit earlier. And I think one of the things that COVID has shown is that the medical community can really bind together and share information in a rapid way. So just as Italy and China learn things, then they pass that on to us, then we got it, we're passing it on to other parts of the country. So it's really banding together, which is great. But yeah, it did alter the way that we approach our patients. We switched a lot of people to oral-based therapies to minimize their interactions with the healthcare system. And that means using drugs that patients may be very familiar with, like Revlimid and pomalidomide (Pomalyst), using drugs like cyclophosphamide (Cytoxan), which many people may get as an intravenous, but as pills.
And then some lesser use pills, like panobinostat (Farydak) and selinexor (Xpovio). The other thing that we did apart from, as you mentioned, switching over Velcade, sorry, switching over Darzalex to the subcutaneous, is holding it for patients. The reality is the half-life of the drug is very long. So if you're already getting monthly, and you need to skip a month or two, the drug does not simply disappear over a matter of days. It takes quite a bit of time.