Treatment Goals and When to Initiate Therapy at Relapse

When we think of the goals of treatment and when to initiate treatment at relapse. We first want to understand what type of relapse a patient is having. It's not unusual to have what we call a biochemical relapse, where those numbers start to come up a little bit, but we don't always have to do anything for that.

Our goals are we want to re-establish disease control, but we also want to maintain that quality of life for our patient and improve overall survival. We don't want to start treatment too early before it's time, but we also don't want to wait too late until they're totally symptomatic.

We think about in that asymptomatic, we've got a little blip in the number, and maybe we've seen it two times or more. We don't react to one number. We consider observation at that point, but we monitor closely. We might start looking at labs a little more frequently than we were before. For that asymptomatic though high-risk patient or rapid progression, most of us are going to go ahead and treat these patients. Tiffany, I think you would agree with that. We're not sitting around on a high-risk patient.

Tiffany Richards (MD Anderson Cancer Center): Exactly. Yeah.

Novel Therapies in Multiple Myeloma

Charise Gleason: Then your patient that's symptomatic or has developed extramedullary disease, you got to go, and the good news is lots more options. It's interesting because for years we've shown you the chart that started at 2003, coming up with all those new therapies, but really, since 2015, you can see how the treatment landscape has really changed.

We started with daratumumab in 2015, and it seems like we've had Dara forever. Then we had belantamab, which was there and then withdrawn, but you can see in 2025, it came back, isatuximab, then we went to our CAR Ts. We have ide-cel, cilta-cel. Then, our first bispecific antibody that was approved, teclistamab.

All that around that 2021, 2022. Then 2023, we have elranatamab, talquetamab, and then, as we said, belantamab got approval again. Then linvoseltamab was approved, hard to believe, almost a year ago. Then now the combination, which we'll talk about more, but pay attention to that one, teclistamab and daratumumab in that relapsed setting. Lots of options and lots of work for all of us to do and understand.

Amazing Success in Immunotherapy for MM

When you look at response rates, you can see those traditional standard of care therapies that we've had. Then look at these response rates as they jump up with these newer therapies. We have patients - for years, we showed this diagram showing you the further out you got, the less response you had, but that's not what we see with these newer therapies.

We've got patients who weren't in remission or went years and years or 14 years out, and we suddenly give them a bispecific antibody or a CAR T, and they go into remission. I think that's been life-changing for our patients, but you can really see how patients are responding to these therapies.

Bispecific Antibodies in MM

What is a bispecific antibody? You can see below that teclistamab, elranatamab, and linvoseltamab hit the same targets, so CD3 and BCMA, so that B-cell maturation antigen. Then talquetamab has a different target. We'll talk a little bit more about that. You've got a CD3-targeted bispecific that recruits T cells.

These are what we call off the shelf. We don't have to send these cells off to be changed. This is something we can move pretty quickly with the bispecific on a patient. It takes one arm is the bispecific molecule binds to the CD3. That's the antigen on T cells. The other arm binds to the tumour-associated antigen that lives on that plasma cell. It's either BCMA in these cases or a GPRC5D. By binding those together, it leads to cell death in a different way, using the patient's immune system.

Targets for Bispecific Antibodies Therapy in MM

Let's talk a little bit more about those targets. BCMA lives on normal and malignant plasma cells. Every treatment we do has a different target. We know these are on all plasma cells. It's essential part of the pathophysiology of myeloma. Teclistamab, elranatamab, and linvoseltamab all target that BCMA. Then we have the GPRC5D. Again, these are just the FDA-approved bispecifics.

We're using many more in clinical trials. This one's a little bit different because not only is it detected on immune cells, but also epithelial cells of the skin and tongue. We do see some different side effects with talquetamab than we see because you do get some off-target response, hitting that, and so you'll see some skin and mouth changes. Again, these targets work well, and we see really nice responses for patients, and these side effects are very predictable and manageable. We're going to talk more about that later.

Efficacy of Bispecific Antibodies in R/R MM

Looking at the efficacy of these, you can see how heavily pre-treated these patients were. This is what we did in the clinical trials. Tiffany and I both participated and probably all these trials at our cancer centers. You can median prior lines of therapy were like five. These are heavily pre-treated patients.

You look at the response rates, the overall response rates, 61, 63, 70, high response rates in these patients, and they're durable. These were FDA-approved for patients who had had at least four lines of prior therapy. We're seeing them moved up as well, like we do with any new therapy. We started in that relapsed refractory, and then we start moving it up in our treatment.

Phase I/II MajesTEC-1: Teclistamab in R/R MM

The Phase I/11 MajesTEC trial looked at teclistamab in relapsed, refractory myeloma. You can see 25% of these patients also had high-risk cytogenetics. Median prior lines of therapy were five. We were seeing triple-class penta refractory patients, and 90% were refractory to their last line of therapy. Again, these are patients who, before, might have been to the more end of what we could offer the benefit for these patients. With these drugs, there was an overall response rate of 63% with teclistamab.

Phase II MagnetisMM-3: Elranatamab in R/R MM

The Phase II MagnetisMM trial looked at elranatamab. Again, you had a mix of patients, like you would expect to see high-risk extramedullary heavily pre-treated. You can see the overall response rate in these patients at 75%. We're looking at overall response rate, but also duration of response. I think is really important in these populations and patients that we see these long-term responses with these new treatments.

Ongoing Trials With Bispecific Antibodies in R/R MM

Ongoing trials with the bispecifics, these are that some that we're using on clinical trials right now, cevostamab. You can see it has a different target, so that CD3, but then the FcRH5, this is trials that are going on right now, and the median prior lines of therapy. Etentamig is at what we call the AbbVie trial is looking at CD3 and BCMA in patients, and then teclistamab versus PVd, so pomalidomide, bortezomib, dexamethasone, or carfilzomib dexamethasone on clinical trial. You can see that one's moved up to earlier lines of therapy at that point.

MajesTEC-3: Teclistamab + Daratumumab in R/R MM

We're going to talk about the MajesTEC-3 teclistamab and daratumumab in relapsed patients. I'll ask you too Tiffany, we're so accustomed in that relapsed setting to using daratumumab pomalidomide dex or Daratumumab bortezomib Dex. Then this trial data came out. It's adding teclistamab to daratumumab. The overall survival and the progression-free survival was much higher. Have you guys started changing practice based on this?

MajesTEC-3: PFS and OS

Tiffany Richards: Yeah. I think we're starting to utilize more teclistamab and Dara, depending on the patient, obviously. If they're CAR T eligible, we would do CAR T before it, but for patients who might not be, or maybe they don't have the resources to be able to stay to get CAR T, then we would be looking at doing teclistamab and dara.

Charise Gleason: We're pretty much the same. We've started doing that. You can see when you add to teclistamab to daratumumab, that 636-month progression-free survival and those high rates so much higher. We change our practices based on clinical trials. You really have to think about your sequencing where when you're doing these, because if this is a patient you want to take to a BCMA CAR T, it's like, when do you do which one?

You can see when you add teclistamab, so you want to remember that to daratumumab it significantly improved the progression-free survival versus daratumumab pomalidomide and daratumumab bortezomib dexamethasone, and greater than 90% of patients progression-free at six months, and most sustaining a benefit for three years.

MajesTEC-3: ORR and MRD

This is the overall response rate and the MRD, which we haven't talked about, so that minimal residual disease. This looked at 10 to the minus five when you look at depth of response and that microenvironment. We started adding daratumumab to our induction regimens because we drive that deeper response. Also, when you combine these drugs, can we get that response deeper? You can see when you add teclistamab with daratumumab, that deeper response that you get with MRD negativity.

RedirecTT-1: Teclistamab + Talquetamab in R/R MM

This is another trial, the redirect trial with teclistamab and talquetamab. In relapsed refractory patients. Can you take two bispecifics that hit different targets and give them both in? The answer is yes, you can do that. In some of us we're doing this off-label. You look at the data, and again, the response rate, always looking at overall response rate and duration. The primary endpoint on this study was dose-limiting toxicities. You can see the response rates were very high in this trial.

The Future of Bispecific Antibodies in Multiple Myeloma

What's the future look like with bispecific? The MajesTEC-7 is looking at teclistamab, daratumumab, and lenalidomide. The DREAMM-10 is looking at belantamab mafodotin, lenalidomide, and dexamethasone. We have the elranatamab, lenalidomide, and dexamethasone trial. Then we have fixed-duration trials.

I think in the future you're going to see a lot more of these type of trials. I think most of our centers are developing them right now. Can you give an assortment of all these things up front? Treat a patient for a period of time, and most of them, I think, the newer trials will be longer than a six to nine-month duration, but then, as we're searching and seeking cure, then can you be off of treatment for a period of time?

That's what this trial did. It discontinued teclistamab after that six to nine month. Then with the plan to resume on progression, so lots of different things. Then how about combining bispecific antibodies with CAR T. We're doing that as well. You had the STEM trial that looks at cevostamab consolidation following BCMA CAR T treatment. You've got the two target approaches as we've talked about. Then we're looking at trispecific, so three target approaches. Lots going on in the clinical research area.

Posttest 1

That's what changes our practice and changes data makes more work for the nurses and the clinicians to understand all these trials that we have available and the side effects that we treat with it. Let's go back to a post-test, or our initial question.

Based on a phase three trial, which bispecific antibody plus daratumumab showed high response rates and a high rate of durable response lasting for three years in relapsed refractory multiple myeloma. Elranatamab, linvoseltamab, talquetamab or teclistamab. We spend a lot of time talking about one of them.

I'm winking. Teclistamab is your answer. It was based on the phase three trial. The MajesTEC trial that added teclistamab to daratumumab. We saw that the 36-month progression-free survival rate was 83.4% with teclistamab dara versus 29.7% with the control, and overall response rate was 89%. Hopefully, everybody got that one right, teclistamab. Tiffany, I'm going to hand it over to you.

Optimal Monitoring and Management of Toxicities Related to Bispecific Antibody Therapy

Tiffany Richards: I'm going to talk about optimal monitoring and management of the toxicities related to bispecific antibody therapy.

Pretest 2

We have a pre-test question number two. You are treating a patient with teclistamab who completed step-up dosing and is on cycle six of standard dosing. The patient presents with new fever and general fatigue. What potential AE do you suspect?

1. CRS;
2. ICANS;
3. Infection; or
4. Disease progression.

Pretest 3

Then our third question is going to be which of the following adverse events would you explain was an on-target toxicity associated with talquetamab and not the BCMA-targeted bispecific antibodies?

1. Dysgeusia;
2. Hypogammaglobulinemia;
3. Neurotoxicity; or
4. Peripheral neuropathy.

Comparing Bispecific Antibodies for R/R MM

We're going to move on to comparing the bi-specific antibodies for relapsed, refractory myeloma. As Charise mentioned, we really have two targets when we're looking at our bispecific antibodies. We have BCMA and then GPRC5D. Talquetamab targets GPRC5D, and the other three target BCMA.

Now, if we look at dosing schedules, step-up dosing schedules, they're all a little bit variable between the four of them. Talquetamab can be given weekly or biweekly, although at our center, we generally start them off with biweekly because it's usually better tolerated. There is some hospitalization after during the step-up dosing, although a lot of centers now are trying to move to outpatient due to the fact that we can now do prophylactic toci, and we're going to talk about that as well. As far as management of side effects.

All of them have similar rates of CRS in ICANS, and same with the neutropenia. Now infection is a little bit less with Talquetamab just because the target is a little bit different. However, because of the GPRC5D being expressed on skin and nail cells, we can see some on-target off-tumour effects with oral nail and skin toxicities.

Current Recommendations for Step-up Dosing When Beginning Bispecific Antibody Therapy

If we think about the step-up dosing when beginning bispecific, as I mentioned, a lot of these would be patients will be admitted to the hospital. Either from 24 to 48 hours. Elra, talquetamab, and teclistamab are all given as subcu injections, whereas linvoseltamab is an IV infusion.

Then we're going to be talking about how we can start reducing the frequency based on responses. With teclistamab and elranatamab, and linvoseltamab, we can begin to go down on the frequency. We can go to biweekly dosing with teclistamab after six months, if the patient's in a complete remission, and then once they get through biweekly dosing at week 10, we can go to every two weeks or every month.

Then same with elranatamab, we can go to every four weeks if they're maintaining a response. Then same with linvoseltamab, which is nice for the patient in and as Charise mentioned, they are actually studies that are looking at hopefully really stopping therapy so that patients don't have to be on this chronic therapy.

BsAb Maintenance: Academic to Community Cancer Care Center

We know that a lot of patients were going to be going back from the academic to community cancer center. When we think about it, we can think of it these four different time points. There's the point where we're talking about treatment and decision-making. The local community practice would be educating the patient and the caregiver about future options and beginning to have that conversation before they're actually at the point of relapse.

I find that helpful when we're talking about if we start to see like a slow biochemical relapse to be able to start having that conversation at that point in time. Then, getting the patient into a nearby center, even if they're not at the point that there may be ready to go on to a bispecific, but at least getting them into the academic center, so that the patient's established and the financial clearance can already start being looked into.

Then, when they get to the academic center, they're going to be undergoing screening, seeing if the patient and the caregiver are eligible, because there is a lot of caregiver support that is needed. Then we can look at it in the preparation and access. Both the community as well as the academic center are going to be addressing these.

Looking at psychosocial barriers, like transportation back and forth, can the patient stay near the academic center, and then mapping out what that's going to look like for the patient and the care partner. Then, doing the education about how to manage these side effects. Then we can move into step-up dosing.

This is going to be done in an inpatient hospital setting, although some centers are moving to more of an outpatient way of giving the bispecifics and then managing and monitoring for adverse effects. A lot of times, after the patient completes that first cycle, and if they're doing well, then the academic center can hand off to the community cancer center.

There needs to be a discussion and what that's going to look like, how often to give the drug, when you're going to start backing off, and then also rescreening for barriers and then doing that one-on-one hand-off to the community center. Then, when the patient gets back into the community, making sure that everything is set up, that you're continuing to monitor and manage those adverse effects, and then coordinate as needed. Follow up with the academic center so that this way the patient cannot have to worry, like, oh my gosh, is the academic center going to be communicating with my local oncologist? Charise, how do you handle that transition of care?

Charise Gleason: We reach out to the local oncology office, and then we send records and recommendations. I can think of a patient that I saw this week who needed to start on IVIG, needed to start on romiplostim, and it's like, let's use your local physician to do that. They're going to start dosing you as well. I think we're seeing more of this go back to the community physician, right?

CRS: Clinical Manifestations and Treatment

Tiffany Richards: Yeah. That coordination is so essential because it helps really alleviate anxiety that the patient may have. If we think about CRS, most of the bispecifics, the CRS is going to be about grade 1 and grade 2, and we're going to talk about how giving prophylactic toci really actually decreases the incidence of CRS.

The CRS constellation can be fever, myalgias, fatigue, headache, hypotension, neurologic changes, dyspnea. I would say for the most part we're seeing fever, maybe some hypotension, and maybe some hypoxia, although it's mild. Generally, are not seeing a lot of grade 3 or grade 4 as far as management. If they've already received tocilizumab as prophylaxis, then we generally would consider adding dexamethasone potentially. You can give another dose of tocilizumab, but it does have a long half-life. A lot of times, for these patients, we might give them some steroids.

CRS: Incidence, Timing, and Severity

If we look at the incidence and timing with the bispecific, so anywhere from 46% to 72%. Again, mostly grade 1 and grade 2, if you look at the bottom of the slide, you can see that really the grade 3 or grade 4 CRS incidence is minimal. Median time to onset is going to be about two days. Although with Linvoseltamab it's going to be sooner.

That's probably because it's given IV, whereas the other three are given as subcu administration. Median duration is going to be about two days, whereas linvoseltamab is going to be less. Again, it probably just has to do with whether a drug is being given a subcu versus being given as an IV infusion.

MajesTEC-1: Longer-term Data on Prophylactic Tocilizumab for CRS With Teclistamab in R/R MM

In the MajesTEC-1, there was a small cohort that received prophylactic tocilizumab to help mitigate. There were about 24 patients, and they were given toci 28mg/kg IV administered less than four hours before the first step of dosing. If you look at the patients who received the prophylactic toci versus those who didn't, you can see the dramatic difference.

72% of patients develop CRS that did not receive prophylactic toci, whereas those who did receive it was only 25%. We can see this improvement in the rates of CRS. The great thing is it didn't impact the overall response rate. 72% versus 63%, and in fact, the response rate was a little bit higher in those patients who received toci.

Prophylactic Tocilizumab

There is another study that looked at prophylactic toci again, 8mg/kg over an hour prior to step up dosing one. Then they received their first dose, and that was one hour after receiving it. If we look at the overall response rates, again, no difference between the registrational trial versus the present study.

Then, if we look at the rates of CRS in the present study versus the trial comparator, again, reduction in the rates of CRS. What this tells us is, is that we can give prophylactic toci. We improve patients outcomes, because we're not going to see those same rates of CRS, and it allows us to still get the same benefit as far as the efficacy of the drug. I think this is really going to allow us to move to prophylactic toci. I know at our center we are now giving prophylactic toci, and I think Charise at your center, you've been doing this for a while now.

Charise Gleason: We have. We started our bispecific outpatient program over a year ago. Before we even had this clinical data, we started giving the prophylactic toci. It's worked really well for us.

Managing CRS With Bispecific Antibody Therapy

Tiffany Richards: When we're managing CRS, if they get grade 1, we're going to hold therapy until the CRS resolves. As in the monumental one protocol. They could consider tocilizumab. If they get grade 2, you're going to hold until the CRS resolves, and then you want to again make sure that you're monitoring that next dose for about 48 hours.

Really, you're going to hold therapy until the CRS resolves, and then you're going to monitor them closely for that 48-hour time period. Then you can consider administering steroids, corticosteroids at grade 2 or higher.

Outpatient Model for Administration of Bispecific Antibodies: AE Management

If we think about moving to an outpatient model for administration of the bispecific antibodies, there really needs to be a lot of patient education.

Making sure I always like to say the right patient for the right model, because you might have some patients that they might not be very good with checking their temperature every eight hours, or maybe they don't have a caregiver. I think we need to think about that in terms of we're seeing more people that are remaining single, or they're not having children.

As we're thinking about this, we can't always assume that every patient has a care partner. Patients need to be monitoring their temperature every eight hours while awake or at the onset of new CRS or ICANS symptoms. They should have a care partner to help monitor for changes in neurologic function, because the patient's probably not going to recognize that.

Then, if they have fever or mental status change to either take their PR and medications and present to the emergency center. If they have grade 1 CRS giving, they will receive tocilizumab over one hour, and then the patient is monitored for eight hours and discharged home if the symptoms have resolved. Then, if they have persistent grade 1 or if they progress to a grade 2 CRS, then they're going to have to be admitted, or if they have any signs and symptoms of neurologic toxicity.

Neurologic Toxicity

If we think about neurotoxicity. The main three types are headache, peripheral neuropathy, and ICANS. The rates of ICANS is low with the bispecifics, anywhere from about 3% to 9%, and again mostly grade 1 or grade 2. Other non-ICAN-related toxicities that they saw was headache and peripheral neuropathy. These patients do need to have ICE scores. We're going to talk about that. We're going to talk about management of ICANS.

ICANS: Clinical Manifestation

How do patients present with ICANS? They could have changes in orientation. They may not be able to follow commands. They may have changes in handwriting. They might have decreased level of consciousness. When we think about the ICE score, it's really looking for all of those areas. As far as treatment, grade 1 would be supportive care. Then, moving to grade 2 is when dexamethasone would be started. We wouldn't give tocilizumab unless it's being accompanied with CRS.

Grading and Managing ICANS: ICE Scoring Assessment

When we're thinking about how to identify ICANS. We're going to calculate an ICE score. We're going to ask them orientation, naming, following commands writing attention. Then they're going to get a score. If they have an ICE score of 7 to 9 and they awaken spontaneously, we're going to hold therapy until the symptoms resolve.

If they move into a grade 2, we're going to start to administer dexamethasone and consider starting an anti-seizure medication. Then obviously if they get to a grade 3, we're going to increase our interventions, and make sure that we're closely monitoring them. Probably get some brain imaging as well.

BsAB Therapy's Infection Risk

I would say with the bispecific, the infection risk is really what's so important that we're thinking about in these patients due to the risk of infection. It's not just that they have infections, but they have a lot of grade three grade 4 infections, and the majority of the infections that the patients received on trial were actually grade 3 and grade 4.

You may be thinking like, well, why is there such a high infection risk with the bispecific antibodies? Well, one, we have patient-related. They develop impaired humoral immunity. Then they also develop significant hypogammaglobulinemia. They're already coming into treatment oftentimes with some degree of hypogammaglobulinemia, because of the fact that there are already received prior treatment, these patients have received already at least four prior lines of therapy. Then there's the myeloma-related.

They have T cell dysfunction. They have CRS risk. Then we're giving them immunosuppressives or supportive medications, toci, corticosteroids. These patients have already received a lot of steroids already by the time they get to the buy specifics, and then we have the treatment-related. We see B-cell aplasia in these patients. Then the continuous therapy that patients are experiencing.

Class Effect: Incidence of Infection With Bispecific Antibodies in MM

What about the risk of infection? If we look at the BCMA-directed therapies, about three-quarters of patients developed infection. Half the patients it was a grade three or grade 4. In the studies with talquetamab, we see less risk of infection. Only about 59% of patients. Then the grade 3, 4 was reduced down to 20%. These patients remain susceptible to infections while they're on the bispecific antibody, and particularly in those patients who are receiving BCMA, directed by specifics.

IVIG Reduces Risk of Serious Infections

What is the role of IVIG? If we look at the effect of IVIG on infection rate, this was a retrospective study that was conducted at Mount Sinai in patients who receive BCMA targeting bispecific antibodies, and IVIG reduced the grade 3 to 5 infections bacteria, whether it was bacterial or not. We know that IVIG works. At our center, we have moved to giving IVIG every month regardless of the IgG level, just due to the risk of infection. Charise, how are you utilizing IVIG in your patients?

Charise Gleason: The same. We give it to everybody, and NCCN guidelines have changed as well. I think some especially of our community partners had some challenges getting it approved at first. I'm not hearing that that's a problem any longer for people.

Effect of IVIG Prophylaxis on Infection-Free Survival in Recipients of BCMA-Directed Bispecific Ab for MM

Tiffany Richards: This study looked at IVIG prophylaxis on infection-free survival in patients who received. You can see that the all-grade infection, the fraction free survival was three months versus 7.7 months. It even saw a dramatic more difference in grade 3 grade 4. In fact, grade 3 infection-free survival was 7.5 versus 14 months.

The patients who are receiving IVIG every month. IVIG does make a difference. It's really critical. Cannot stated enough that patients should be placed on IVIG prophylaxis. At our center, we also do herpes zoster prophylaxis and pjp prophylaxis as well, just to help mitigate some of this.

Consensus Recommendations for Managing Infections in Patients With MM Receiving BsAB Therapy

There are some consensus recommendations for managing infections in patients. As I mentioned, we utilize herpes zoster prophylaxis either with valacyclovir or acyclovir. All patients should be screened for hepatitis B because there is a reactivation risk. If there are hepatitis B core antibody at our center, we do place them on entecavir. Monthly IVIG for the duration while they are on that. Administer G-CSF in patients who develop neutropenia. PJP prophylaxis for all patients in making sure patients are up to date on all of their vaccinations. Charise, do you do anything different?

Charise Gleason: No. All of this is the same.

Fatigue With BsAbs

Tiffany Richards: What about fatigue? I think fatigue in patients with myeloma is probably what we see most commonly. The fatigue can be caused by the treatment. They could be anemic. Cancer-related fatigue is really a burden on patients, that leads to trouble concentrating. They may develop loss of strength because they're not being as active as they were.

Rates of fatigue were anywhere from a third to 43% of patients, any grade and grades rates of grade 3 were as high as 6%. Fatigue initially worsens and then returns to baseline. That's probably because we're spacing it out. We know that for cancer-related fatigue, the best intervention is going to be physical activity and exercise.

Although the one thing is, whenever a patient presents with fatigue, we need to be making sure that they're not having depression. Patients may not even realize that they're depressed. Other things you could use is massage therapy and then cognitive behavioral therapy, and bright white light therapy.

Bispecific Antibody REMs Program

All patients, all bispecifics have a REMS program, and so prescribers must be certified in complete training, and they must counsel patients receiving all the bi-specifics on the risk of CRS and neurologic toxicities, and they have to be given a patient wallet card. Then pharmacies and healthcare facilities must be certified with the REMS program.

Posttest 2

What about management of GPRC5D?

Pearls for Managing GPRC5D-Associated AEs

As I mentioned, talquetamab has some on-target off-tumour effects. We can see dysguesia. We see dry mouth. We can see skin reactions. We can see nail changes. For Dysgeusia, just talking to patients, setting them up with a nutritionist. Really, the thing that helps the most is the reduced dose intensity once they get a response. For dry mouth, making sure they're staying adequately hydrated, making sure that they don't have any other infection in their mouth.

We actually had a patient who was on talquetamab and had mucositis, and we actually cultured it. She actually had a bacterial infection. We were able to give her some antibiotics, and it cleared it all up. Sometimes you really do need to make sure that it's just not mucositis. How we usually think about it, but that we're making sure that it is nothing else going on.

As far as the skin reactions generally occur within that first month. You can do - we use Vanicream. We use ammonium lactate. They need to be utilizing sunscreen. Generally, that rash occurs within that first month, and then we really don't see too much of it subsequently. Then we can see nail changes. We place all patients on nail hardener. Then, vitamin E cuticle oil as well.

Posttest 2

We're going to go to our post-test questions now. You were treating a patient with teclistamab who completed step-up dosing and is on cycle six of standard dosing. The patient presents with a new fever and general fatigue. What potential AEs do you suspect?

1. CRS;
2. ICANS;
3. Infection; or
4. Disease progression.

The correct answer is infection, because the patient is on cycle six of standard dosing. We would not expect to see CRS at that point in time. We would really want to be cluing into the infection, particularly with the risk of infection with biospecifics.

Posttest 3

Post-test question three. Which of the following adverse events would you explain was a unique on-target off-tumour toxicity associated with talquetamab and not the BCMA-targeted bispecific antibodies?

1. Dysgeusia;
2. Hypogammaglobulinemia;
3. Neurotoxicity; or
4. Peripheral neuropathy.

The correct answer is going to be Dysgeusia because it targets GPRC5, D is the target for talquetamab.

I am going to turn it back over to Charise.

Optimizing Nursing-Led Communication and Patient Education to Mitigate Risk and Improve Outcomes in Patients With MM Receiving Bispecific Antibodies

Charise Gleason: We're in the homestretch. We're going to talk a little bit about optimizing nursing lead communication and patient education to mitigate risk improve outcomes in patients who are receiving bispecific antibodies. We've talked about all these antibodies and all these options that we have.

Role of Nurses and Nurse Navigators in Care Transition for Patients Receiving BsAbs

We give them in the academic centers, but we also partner with our community. What are the roles of nurses and nurse navigators in that care transition for patients who are receiving bispecifics? Can't say enough about patient education. Advocating for your patient. This is what nurses do. This is what we do.

That care coordination piece, as we go back and forth, or maybe you're at a community center that's doing it all now, but making sure we get that IVIG started. Those prophylactic antiviral antibiotics in ongoing symptom recognition and management of the patient. Giving them the upfront information, monitoring them throughout.

Having your patient know when to call you to tell you I've got something new, something different. What are those things that we expect early? What are the things we expect later? All of that. I can't say enough about the communication, but that transition care planning. A lot of centers aren't local communities aren't set up to give these to have the things in place.

They might ask the academic center to give that first cycle, and then they take over from there. There's a lot of transition care planning, or even can we partner with our partners in the community that, okay, maybe we gave this dosing, but you're going to give the IVIG. Lots of logistics around this.

Not all patients live close to their community center, either. How can we make sure our patients are getting access to these amazing treatments, but also managing all that comes with it? For Tiffany and I, this is all we do. We see myeloma patients. You might be working in a practice setting where you're seeing all different cancers and treating. There's a lot to think about and a lot to coordinate, but it can certainly be done. I think neither of us can emphasize enough that bispecifics are something that can be done in the community.

Patient-Centered Communication

Patient-centered communication, we think about patient-centered care in our cancer centers. How we talk to our patients, and we've just gone through all these trials and all this information. When we're talking to our patients, we want to use that language that they understand. Make sure they hear that they've confirmed their understanding, and how do they want things explained to them, or what resources do they want?

Do they want to be able to go to the internet? Do they want handouts given to them? When I think of CRS, as Tiffany talked about, most of our CRS are grade 1, telling a patient this is like flu-type symptoms. It's things that make it real for them that they can understand. I think there's a lot of fear around CRS and Tiffany, I'm sure you agree, because what they hear from CAR T it's very different with bispecifics.

That's why we have been able to take these to the outpatient setting. How about emphasizing the importance of new symptoms, when to report symptoms, and encourage your patients and caregivers to ask questions. I ask patients to remember to write things down. They get a limited time with us when we're seeing them in clinic, so bring your questions. Don't hesitate to call. We'll reach out to our patients when they've started on a new bispecific just to see how they're doing. Tiffany mentioned a little bit, a lot of side effects can be mitigated to when you back off the frequency.

Individualizing Education and Risk Mitigation

We do some things a little off-label. I think you're going to find and what the data is telling us that we don't have to give these drugs as frequent, especially once they've responded. We want to remember that we tailor communication to our patient and their literacy, their language preference, and their cultural background.

Do they want their family members more engaged? Do they want more information to go to a family member? If they speak another language, do we have those tools to give them the resources and the explanations, the side effects to look out for in their language? I think most of us with our technology have that ability to do that. We want to provide that education on risk.

Again, what's your best way of learning? Do you want to hand out? Do you want this to go to your patient portal? Do you want us to give you a link that you can go look things up? You want to make sure that education covers the goals of therapy, infection prevention, we can't say enough about that, and that adverse event management.

Successful BsAB Administration Requires a Team of HCPs

Our strategy and patients are also still worried about their disease. All that conversation still goes on. It really takes a team of us to do this. You may not have every member of this team, but we've got our oncologists, our physicians, our APS, our nurses, our nurse navigators. If you have those, I can't say enough about our clinical pharmacist and Sara Scott, who Tiffany talked about pretty much she's our clinical pharmacist at Emory.

It pretty much set up our outpatient bispecific program and then published on it. Our social workers to - sometimes patients need help with a multitude of things, but getting back and forth. Our critical care staff, our emergency department, we're fortunate at my cancer center that we have an immediate care center for oncology patients.

Our goal is to actually try to keep patients out of the emergency department, because it's hard to educate everybody, but that may be the only place your patients can go, so making sure that education has happened in that with that staff to understand the risk of infection, if one of our patients shows up in the ED and then our administrator partners as well, that help us get access and do the things that we do.

Interprofessional Collaboration

Interprofessional collaboration. I think a team approach to taking care of our myeloma patients. it improves that communication. We have to have good communication amongst the team. Good handoffs to our partners in the community. We want to make sure that we're listening to our patients and that their preferences are being considered as well. They're part of the discussion when we start a new treatment. Always keeping that patient in the forefront. Then, what interdisciplinary meetings you have to address the needs of patients? Whether it's a tumour board or a time that you can talk about a specific patient.

Poll 4

Through that quickly, but this is getting us to the end. Have the first question for you. Poll number four. If you'll answer, please rate your level of agreement with the following statement. I am very confident in ensuring communication among all health care providers, the patient and caregivers when a patient initiates a bispecific antibody therapy.

1. Strongly agree;
2. Disagree;
3. Neither disagree or agree;
4. Agree; or
5. Strongly agree.

Tiffany, are you taking this one, or you want me-

Poll 5

Tiffany Richards: I can take it. Do you plan to make any changes in your clinical practice based on what you learned in today's program?

1. Yes;
2. No; or
3. Uncertain.

Poll 6

Charise Gleason: Then, if you'll take a moment to enter a key change that you plan to make in your clinical practice based on this education. While you're doing that, we do have a question.

Q&A

I can read it, and Tiffany, we can talk about this. How do we manage a patient anxiety around CRS and Icans education without overwhelming them or making them afraid to start treatment?

Tiffany Richards: I think that's a great question. I think it's always like this, like back and forth, is you want to make sure that patients are aware of the risk, but you also don't want to make it seem like it's - you don't want to catastrophize it either. I think it's just putting it into terms that they understand how you mentioned, about the flu-like symptoms and what the reality of what they're most likely going to experience.

Charise Gleason: I think sharing that data that most of this is going to be a grade 1, we give tocilizumab as prophylaxis. If you're at a work somewhere where they don't give it for prophylaxis, they're going to give it at first signs of a grade 1. I think reinforcing that this is not the CRS that you heard of with CAR T. We have another question. How should nurses educate patients and caregivers to distinguish expected post-dose symptoms from early signs of CRS or ICANS?

Tiffany Richards: I think that's hard for a patient to be able to figure out, like what is expected versus what is CRS. I usually give them instructions of like when they should go to the emergency room and when they should call. Then tell them, like, let us help you to figure out if there's a question and it's during clinic hours, then you can call. If it's a fever, I always tell them come to the emergency room. For other symptoms, just trying to have the healthcare team figure that out because I think it's really hard for a patient or caregiver to really mesh that out for themselves.

Charise Gleason: I agree, and I think just remember when you're educating patients, the CRS that we see is early and predictable. You're going to see that in that step up if they're having those symptoms. We also, because we do the majority of these in the outpatient setting, we give them instructions of, we send them home with some dexamethasone that we call their pocket dex.

They call in, our team will instruct them to take that, and if they want them to come in, they'll come in to our urgent care center, immediate care center. I think it's very different. It's early. We know when we're going to see it, and you're just not going to see it after that as you get into subsequent dosing. Another question. How often should ICE scoring be performed during step up, and who on the care team should be responsible for documenting it?

Tiffany Richards: At our center, if they're in the hospital, the nurses do it twice a day. As far as at home, I usually tell them to do it twice a day and then report anything. I would say that, like if they're in the hospital, the nurses are going to be doing that. If they are outpatient, we have a team that sees those patients who are on the bispecifics, and then the APP there is the one that's responsible for doing the ICE scoring.

Charise Gleason: Again, very rare. Typically, if you're going to see it, you're going to see a headache. That's an easy thing to educate a patient on. One of those easy ones to let us know about.