Mary Steinbach:
Hello and welcome to JADPRO's Roundtable discussion on Multiple Myeloma Bispecific Agents in Special Populations: A Case-Based Approach. My name is Mary Steinbach and I'm a nurse practitioner at Huntsman Cancer Hospital in Salt Lake City, Utah, and I am here with my colleagues, Kelley Julian and Kevin Brigle. Kelley, do you want to introduce yourself?
Kelley Julian:
Sure. Thank you Mary. I am Kelley Julian and I work at Huntsman Cancer Institute alongside Mary in our multiple myeloma clinic. I am a clinical pharmacist by training and been practicing multiple myeloma since 2018, so I'm excited to be here today and chat with you all.
Mary Steinbach:
Great, thank you. And then we have Kevin Brigle with us. Kevin and I are colleagues on the International Myeloma Foundation's Nurse Leadership Board. Kevin, can you introduce yourself?
Kevin Brigle:
Sure. I am a nurse practitioner in the Hem Malignancy Clinic at the Massey Comprehensive Cancer Center at Virginia Commonwealth University. So I have a lot to say there and I am glad to be back with you two and talk about our favorite topic, myeloma.
Mary Steinbach:
Yes, indeed. Awesome. So we felt like for today we are going to start with a patient case and as I mentioned, we're going to talk about specialty populations to consider for bispecific antibodies and I'm going to start us off with this case.
I chose it based on a couple of access issues and treatment-related potential that we had to really consider when we talked about a bispecific for this patient.
Our patient is a 50-year-old male. He lives in a rural area. He is a farmer and is responsible for owning and managing his farm. He was diagnosed with lambda light chain multiple myeloma.
It was RSS stage II at the time, and this was back in 2017. We knew then that he had a translocation 11;14 and a 1q gain. Following on what our practice was at that time, he had RVD induction auto-transplant, though unfortunately while on maintenance and after another line of therapy in 2023, he had a very large relapse, and I say large relapse because his presentation was with secondary plasma cell leukemia at this time, and concurrent renal failure, so he became dialysis-dependent back in '23.
We were able in 2024 to give the patient cilta-cel and thankfully he had a very quick response to that though unfortunately after about 9 months, another progression.
So that brings us to November of 2024 and early progression after cilta-cel we know can be a really high-risk feature. And so, we decided to start the patient on talquetamab.
As you can imagine, living in a rural area, we had to really organize ourselves well to get this patient back for ramp up.
Kevin, do you have any experience starting patients who have been on dialysis with bispecific antibodies, with any of them?
Kevin Brigle:
Yes, we have experienced, I think a lot of people do actually at this point in time, not originally, but we have patients who started on teclistamab who've been on dialysis, not anyone that I'm aware of yet on talquetamab, but for our teclistamab patients it's really gone quite well and there's actually data in the literature to support that as well. There's been a nice published article talking about that. And in addition, what we had just originally done before there was data published was just make sure the patient, whenever they dialyze, we would have them dialyze hopefully the day prior to teclistamab and then if not, the day after. But we would try and delay that just by a couple of days.
Mary Steinbach:
Yes, that's a great point. As we all know, patients who are on dialysis are often excluded from clinical trials, so we do, as Kevin mentioned, have some good real-world data, a lot of patient case reports that have been published at this time about getting what are the increased toxicities for patients who are dialysis dependent. And the short of it is there really is not.
I think the challenge lies in organizing the schedule for ramp-up, patients who are on dialysis depending on what their dialysis schedule capabilities are, and that's dependent upon where you live, or the patient lives. Most likely these people will get admitted for their ramp-up. Even if at Huntsman we have an outpatient program for ramp-up, but someone who's on dialysis we would just admit, and I think our practice, and Kelley, you can correct me if I'm wrong, is to dose the bispecific following dialysis. So whether it's the day after or even later that afternoon if that's what the constraint has to be.
Kelley Julian:
Yeah, exactly. We've done it both ways, but I think as long as you give it post-dialysis, even if it's same day, these bispecifics are kind of large molecular-weight molecules and they are not dialyzable. So doing it post-dialysis, whether that's same day or the next day, kind of prevents those theoretical swings in the levels, and we think reduces the risk of things like CRS and ICANS, which thank goodness, because that's what we're most concerned about with these patients who are ramping up.
I will say the MonumenTAL-1 registration trial excluded patients with creatinine clearance of less than 40. So, we're really glad to have the real-world data that Kevin mentioned here to kind of direct us.
Mary Steinbach:
Perfect. And then for all patients on bispecifics, you want to be aware of the adverse side effects. And so for someone like this patient who receives talquetamab following a BCMA, and as I mentioned it was within a year still from that BCMA CAR-T so the type of monitoring that we did for this patient still encompassed their 1 year post CAR-T, so this is a patient who is getting IVIG monthly and then you want to watch for kind of the BCMA infection potential, still follow CMV if that is indicated in the patient.
At this point in time, our practice at Huntsman is we're going to follow CMV in talquetamab patients or non-BCMA patients if they have a positive CMV-PCR at any time. But if they start off negative, then we aren't going to follow CMV in these patients anymore.
Do you guys have any different practice, Kevin, in terms of infection monitoring for someone on dialysis or infection prophylaxis?
Kevin Brigle:
Probably not so much infection prophylaxis. I think pretty much what you've described is exactly right in terms of CMV monitoring for patients who are negative, then very much like you do for patients who are positive, we move that monitoring up a little closer, and some of those patients may need to be on suppression that as well.
Mary Steinbach:
And so this patient did very well for a period of time on talquetamab though unfortunately we saw a rising light chains and again, in someone who is dialysis-dependent, they're going to have a higher threshold of light chains.
And so there was an article published about what the baseline numbers should be in patients with renal failure when you're using light chains to monitor disease status. And so you just want to consider, because obviously patients with renal dysfunction secrete more light chains than those without.
Anyway, this patient did progress a little bit and what we did at that time was add pomalidomide to the talquetamab and we did this early because knowing a quick progression after CAR-T, and then now on kind of our last best great option of talquetamab and there is some early data that adding an IMiD to talquetamab can improve its efficacy.
Thankfully, with talquetamab, this patient did not have a lot of very serious side effects and so has been able to eat and drink normally, didn't have a skin rash, and really has done okay otherwise.
So this patient, after starting the pomalidomide, did have another improvement in his light chains and again, has done well. And if we remember back to the beginning of the case, one of the important things for this person's life is being able to manage their farm.
And so back in a stringent CR, we began to discuss how to reduce talquetamab and often we talk about how to delay dosing or decrease or increase the amount of time between dosing with talquetamab when people have adverse reactions. But here we addressed it really just in the effort to improve this patient's quality of life.
Kelley, what are your thoughts about how to dose de-escalate when quality of life is an issue and you know the patient's in a good response already?
Kelley Julian:
Yeah, thanks, Mary. I think I've seen us do this one of two ways. Ideally, the patient's response is a VGPR or better, and we start having these discussions, especially if the side effects are overwhelming, I think. So our practice at Huntsman is to do the every-2-week dosing of 0.8, and we typically try to reduce that to monthly dosing if the patient is able.
I have seen us prior to that if the dysgeusia or things like that are overwhelming for the patient. We have probably one or two patients where we cut the dose in half to the 0.4 and kept it on every 2 weeks until they got into that response and then we space it out even to monthly from there.
So it really depends on what's happening with the patient.
Obviously for someone like this, in the case that we've been discussing, being at home is super important, so coming less frequently is most ideal.
But I think this is largely somewhat of an art and provider preference based on their discussions with the patient. As long as we know the safety is maintained, and especially if they're struggling with infections or things like that, it can really dictate how we adjust.
Mary Steinbach:
Perfect. Thank you.
So that brings us to the end of our discussion. I would just like to highlight again that we reviewed a patient who is on dialysis, and lives far away from a treatment center and was able to successfully receive talquetamab. I think my take-home pearl about this is that bispecifics should be dosed following the dialysis session, certainly not right before the dialysis session.
And we know from case reports that have been published and a couple of smaller retrospective reviews that the CRS risk and the risks for ICANs and other adverse events that we're familiar with with the bispecific antibodies seem to be about the same in dialysis patients as they do for others. So no increased safety signals there.
Kevin and Kelley, thank you so much for taking the time out of your day to discuss this with me. For more information and to view other discussions on multiple myeloma, please visit JADPRO online at jadpro.com. Thanks so much, and have a great day.
