BETH FAIMAN: I think we should go on with another case. This is so much fun, I want to keep it going, right? But let's do another case.
So, we have a 62-year-old male who had first been diagnosed in 1997 with a monoclonal protein MGUS and was watched for several years with every 6-month blood and urine studies. Remember, we didn't have serum free light chains available until 2004. A lot of people that are younger might not be aware of that fact, but the Bence-Jones protein was assessed, as well as the M spike. And eventually this patient progressed to multiple myeloma needing treatment. And that patient started on a clinical trial with thalidomide and dexamethasone, and after the induction they got a tandem stem cell transplant. And then they went on thal-pred maintenance, which was a very common clinical trial that was available in the early 2000s. And so, after a period of remission, that patient progressed, had developed some pretty significant peripheral neuropathy from thalidomide, but the disease was in control, so that was good, right? Back then, we know more about pushing people with neuropathy, but anyhow, then they had lenalidomide/dexamethasone, then bortezomib/Cytoxan/dexamethasone. SubQ became in favor of the bortezomib, which led to that therapy. And again, a 10-year history of treatment.
So, now at this point, this poor 62-year-old is kind of beaten down by therapy, it's not that first or second relapse where we really have a plethora of options we can discuss as we've talked about before. Now, we're in a place where we really need to, as providers, really share our knowledge on clinical studies and what we think is best for the patient. Because now this patient's refractory to bortezomib, carfilzomib, they've had thal, lenalidomide and pomalidomide, enoblituzumab, and even a clinical trial with panobinostat and ixazomib. So, now what do you do after all these different therapies? The patient does not like the idea of an implanted Mediport and they have bad veins. So, a subcutaneous therapy would be ideal, but unfortunately, that individual has some significant neuropathy from thal and bortezomib earlier.
So, again, we've discussed the use of daratumumab in the newly diagnosed relapsed and refractory setting. Daratumumab can be given in combination with bortezomib, melpha, and prednisone. It can be given in combination with thal and dex and bortezomib, and len-dex, and all these different opportunities for giving that. But based on the data from the COLUMBUS study and the PLEIADES study, there were 263 patients actually in one of the studies which were given this daratumumab with the hyaluronidase, which I can't ever pronounce, in combination with bortezomib, melphalan, and prednisone. And, again, it's also been studied subcu dara in combination with lenalidomide and dexamethasone as well. So, in various combination therapies.
So, how is it given? It's given subcutaneously, and it was non-inferior to the IV study. In the major trial, the phase III trial, there were 522 patients with a median follow-up of 7.5 months, and you can see in this table highlighted on the slide that the subQ had median progression-free survival of 5.6 months versus 6.1 months, and that was not statistically significantly different. Looking at the pharmacokinetics, how it runs through the body, it was pretty much similar in the intravenous and the subcutaneous groups, and it tended to be again effective with very few side effects.
What's so nice about the daratumumab is that the median duration of administration is like 5 minutes, compared to the infusion time of 7 hours for the first dose. So, all these years we've been telling people, “come to the clinic at 7 AM, you might be here 'til 7 PM, pack a lunch, and then you're gonna get this long therapy, but then wait, you got to get a driver because you might be sedated because of the corticosteroids and the diphenhydramine we're going to be giving you to prevent a reaction.” So, you go from this long infusion time, and when this becomes readily available in clinics, I think it's a much different discussion as to the therapy. I don't know about you, Donna and Tiffany. I'll ask Donna first what your thoughts are. Whenever I say daratumumab equals 12 hours in the clinic, what's your feedback?
DONNA CATAMERO: it's the same, and it's more on an operational standpoint. Patients are in that chair for, like you said, could be up to 12 hours, and some clinics are not open, they're more of a 9 to 5. So, I think this will give us more of a chair availability for patients. And I think too that we saw fewer adverse events, the infusion reactions. So, it's very well tolerated. I think this is a game-changer in the way we give daratumumab. The only downside I would see is that, you know, we all have those frail patients with no subcutaneous fat that might not be the best candidate for a subq injection. That's the only downside I can see.
FAIMAN: Tiffany?
TIFFANY RICHARDS: I would agree. I think this is really definitely going to be such a huge improvement for our patients. I know at our center, like our patients right now can't go to any of the satellite centers around Houston, because that first infusion time is so long. So, they have to come down to our main campus. And so now we'll be able to give this their first injection right out at our regional care centers, and I think that's going to be very appealing for patients, and I think this is going be huge for patients as far as the amount of chair time that they have to spend at the clinics.
FAIMAN: Absolutely. And for our case study, who's had multiple prior therapies and doesn't really want to get an implanted Mediport at this stage in the game, I think it's a nice option for them.
There are other therapies such as selinexor, which is not easily tolerated, but it is still an excellent option for some people. That therapy is given orally, but as Donna and Tiffany are very well aware, patients need to be monitored. They can get hyponatremia, so, you know, we worry about telling them to eat salty snacks and they can have a lot of weight loss and GI issues. We have put a paper out with recommendations on side effects for that, but maybe the patient doesn't want to accept all of these side effects. There's not a good clinical trial.
The subQ dara incidence of infusion reaction was 7.5% in the clinical trial, and it's about 50% in patients that get the infusional daratumumab. In my experience, we do the best we can to premedicate them in the office. If they have a lot of breathing problems, I do recommend loratidine 10 mg, and I also recommend on top of that montelukast 10 mg, just for the first couple of weeks. I think everybody has their own. But I've not done this in any of the clinical trials with the subcutaneous. Do you ladies have any experience with additional pre-meds for that first IV dose or any experience with those same pre-meds with the subQ formulation?
CATAMERO: Beth, we actually use the same regimen, and we've seen a decrease in the incidence of more respiratory issues with patients, so I think with the addition of those two medications, the daratumumab was better tolerated.
RICHARDS: Yeah, I do too. We do the same thing, and I think we haven't seen a lot of the breathing-related infusion-related reactions, and I usually tell patients that, you know, make sure to report the initial symptoms of infusion-related reaction, rather than waiting until they can't breathe, and, I think, you know, our patients are very savvy, and I think generally speaking, a lot of our patients do what we tell them to do.
